Vincristine induced cranial polyneuropathy
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《印度儿科学杂志》
Abstract
We describe a 5-year-old girl showed recovery of vincristine induced cranial polyneuropathy with pyridoxine and pyridostigmine treatment. A 5-year-old girl was diagnosed preB cell Acute Lymphoblastic Leukemia (ALL). She received chemotherapy according to the previously described modified St. Jude total therapy studies XIII. Five days after the fourth dose of vincristine, she presented with bilateral ptosis. Neurological examination revealed bilateral ptosis, and complete external opthalmoplegia with normal pupillary and corneal reflexes. She received 3.8 mg cumulative dose of vincristin before development of ptosis. A neuroprotective and neuroregenerative treatment attempt with pyridoxine and pyridostigmine was initiated. The bilateral ptosis markedly improved after 7 days of pyridoxine and pyridostigmine treatment and completely resolved after two weeks. The both agents were given for 3 weeks and were well tolerated without any side effects. During the follow up period we did not observe residue or recurrence of the ptosis.
Keywords: Vincristine; Ptosis; Treatment
How to cite this article:
Bay A, Yilmaz C, Yilmaz N, Oner AF. Vincristine induced cranial polyneuropathy. Indian J Pediatr 2006;73:531-533
How to cite this URL:
Bay A, Yilmaz C, Yilmaz N, Oner AF. Vincristine induced cranial polyneuropathy. Indian J Pediatr [serial online] 2006 [cited 2006 Jul 14];73:531-533. Available from: http://www.ijppediatricsindia.org/article.asp?issn=0019-5456;year=2006;volume=73;issue=6;spage=531;epage=533;aulast=Bay
Vincristine is a vinca alkaloid used in combination with other agents in the treatment of solid tumors, lymphoma, and leukemia.[1] Severe vincristine toxicity is uncommon: in a detailed review, only 3.6% of the patients in POG 9201 had significant toxicity reported, with only 2.9% of patients having any alteration in therapy.[2] The dose limiting toxicity of vincristine is its neurotoxicity. The pathogenesis of neuropathy is explaned by vincristine causes structural changes in the microtubules of peripheral nerves and interferes with axoplasmic transport.[3] It manifests as loss of deep tendon reflexes, neurotic pain, paresthesias, and wrist and foot drop. Less frequently, cranial nerve palsies, transient cortical blindness, oculomotor nerve dysfunction, jaw pain, facial palsy, sensorineural hearing loss, and laryngeal nerve paresis have been attributed to vincristine.[3],[4]
We describe a 5-year-old girl who showed complete recovery of vincristine induced cranial polyneuropathy with pyridoxine and pyridostigmine treatment.
Case Report
A 5-year-old girl was diagnosed preB cell ALL (FAB L1 subtype). She received chemotherapy including prednisolone (60 mg/m 2), L-asparaginase (10.000 U/m 2), vincristine (1,5 mg/m 2), and daunorubicin (25 mg/m 2) with triple intrathecal therapy according to the previously described modified St. Jude total therapy studies XIII with minor modification including high-dose methylprednisolone.[5] Five days after the fourth dose of vincristine, she presented with bilateral ptosis [Figure - 1]. There were no previous clinical symptoms of neuropathy and no positive history for inherited neuropathies. Neurological examination revealed bilateral ptosis, and complete external opthalmoplegia with normal pupillary and corneal reflexes. The remaining physical findings were normal. Laboratory evaluation revealed the following values: hemoglobin, 8.5 g/dL; platelet count, 70 000/mm 3; white blood cell count, 2 600/mm 3 aspartate aminotransferase, 138 U/L; alanine aminotransferase, 81 U/L; lactate dehydrogenase, 914 U/L; triglyceride 212 mg/dl and total bilurubin 2.2 mg/dl. Cerebrospinal fluid examination and cranial MRI was normal. We would like to emphasize that the development of ptosis in the patient receiving a chemotherapy regimen including vincristine should raise the suspicion of toxic cranial neuropathy. She received 3.8 mg (6 mg/m 2) cumulative dose of vincristin before development of ptosis. She did not receive further doses of vincristin ptoziz düzelene kadar. A neuroprotective and neuroregenerative treatment attempt with pyridoxine (150 mg/m 2 p.o. BID) and pyridostigmine (3 mg/kg p.o. BID) was initiated. The bilateral ptosis markedly improved after 7 days of pyridoxine and pyridostigmine treatment and completely resolved after two weeks [Figure - 2]. The both agents were given for 3 weeks and were well-tolerated without any side effects. During the follow up of 2 months we did not observe residue or recurrence of the ptosis.
Discussion
Vincristine-induced neuropathy is usually mild, severe complications including partial or total paralysis was reported in rare cases.[3] Symptoms usually appear 2 to 19 weeks after the commencement of vincristine.[4] Vincristine neurotoxicity is more severe under the following circumstances: if more than the recommended maximum cumulative dose of 30 to 50 mg is given, if the patient is hypersensitive to this drug, if there is pre-existing liver dysfunction or a hereditary neuropathy, and if other drugs such as allopurinol, erythromycin, isoniazid, mitomycin C, phenytoin, and itraconazole are concomitantly used.[6] In our patient we did not use high dose vincristin and the other concominant accelerating drugs.
The definitive diagnosis of a drug-induced neuropathy depends on the exclusion of other etiologies that may produce a similar clinical picture. The following characteristics of the present case support our initial diagnosis of vincristine-induced neurotoxicity as the cause of ptosis: (1) the time course of ocular changes in relation to the therapeutic schedule with vincristine; (2) resolution of symptoms after pyridoxine and pyridostigmine therapy; (3) normal CSF findings (ie, no atypical cells); and (4) absence of other parenchymal brain lesions on MRIscan.
Several cases of severe neurotoxicity associated with vincristine use in patients with underlying and asymptomatic Charcot-Marie-Tooth syndrome have been reported.[2],[7] Our patient returned to a normal neurologic status in a brief period of time, which is not a typical feature of vincristine neurotoxicity complicated by hereditary motor and sensory neuropathy type 1, where recovery is slow and incomplete.
In animal studies pyridoxine has been demonstrated to induce some neuroprotection during intrathecal administration of lethal doses of vincristine.[8] Pyridostigmine or analogues have been used for enhancement of intestinal motility in patients with atonic bowel due to various causes, and reduction of gastrointestinal motility represents one of the major symptoms of vincristine-induced neuropathy.[9] Recently, Muller et al reported the full recovery of vincristine -associated bilateral ptosis after treatment with high dose pyridoxine and pyridostigmine in a 2 years old child.[10] We used the same treatment regimen in a 5 year old female with ALL who developed ptosis after chemotherapy treatment. This treatment was very well tolerated by a 5-year old girl with no documented side effects. We suggest that pyridoxine and pyridostigmine are safe and effective treatment options in vincristin-induced cranial neuropathy.
References
1. Quasthoff S, Hartung HP. Chemotherapy-induced peripheral neuropathy. J Neurol 2002; 249: 9-17.
2. Chauvenet AR, Shashi V, Selsky C, Morgan E, Kurtzberg J, Bell B Vincristine-induced neuropathy as the initial presentation of charcot-marie-tooth disease in acute lymphoblastic leukemia: a Pediatric Oncology Group study. J Pediatr Hematol Oncol 2003; 25 : 316-320.
3. Moudgil SS, Riggs JE. Fulminant peripheral neuropathy with severe quadriparesis associated with vincristine therapy. Ann Pharmacother 2000; 34 : 1136-1138.
4. Legha SS. Vincristine neurotoxicity. Pathophysiology and management. Med Toxicol 1986; 1 : 421-427.
5. Yetgin S, Tuncer MA, Cetin M et al. Benefit of high-dose methylprednisolone in comparison with conventional-dose prednisolone during remission induction therapy in childhood acute lymphoblastic leukemia for long-term follow-up. Leukemia 2003; 17 : 328-333.
6. Chan JD. Pharmacokinetic drug interactions of vinca alkaloids: summary of case reports. Pharmacotherapy 1998; 18 : 1304-1307.
7. Neumann Y, Toren A, Rechavi G et al. Vincristine treatment triggering the expression of asymptomatic Charcot-Marie-Tooth disease. Med Pediatr Oncol 1996; 26 : 280-283.
8. Jackson DV, Jr., Pope EK, McMahan RA et al. Clinical trial of pyridoxine to reduce vincristine neurotoxicity. J Neurooncol 1986; 4 : 37-41.
9. Battle WM, Snape WJ, Jr., Alavi A et al. Colonic dysfunction in Diabetes mellitus. Gastroenterology 1980; 79 : 1217-1221.
10. Muller L, Kramm CM, Tenenbaum T, Wessalowski R, Gobel U. Treatment of vincristine-induced bilateral ptosis with pyridoxine and pyridostigmine. Pediatr Blood Cancer 2004; 42 : 287-288.(Bay Ali, Yilmaz Cahide, Y)
We describe a 5-year-old girl showed recovery of vincristine induced cranial polyneuropathy with pyridoxine and pyridostigmine treatment. A 5-year-old girl was diagnosed preB cell Acute Lymphoblastic Leukemia (ALL). She received chemotherapy according to the previously described modified St. Jude total therapy studies XIII. Five days after the fourth dose of vincristine, she presented with bilateral ptosis. Neurological examination revealed bilateral ptosis, and complete external opthalmoplegia with normal pupillary and corneal reflexes. She received 3.8 mg cumulative dose of vincristin before development of ptosis. A neuroprotective and neuroregenerative treatment attempt with pyridoxine and pyridostigmine was initiated. The bilateral ptosis markedly improved after 7 days of pyridoxine and pyridostigmine treatment and completely resolved after two weeks. The both agents were given for 3 weeks and were well tolerated without any side effects. During the follow up period we did not observe residue or recurrence of the ptosis.
Keywords: Vincristine; Ptosis; Treatment
How to cite this article:
Bay A, Yilmaz C, Yilmaz N, Oner AF. Vincristine induced cranial polyneuropathy. Indian J Pediatr 2006;73:531-533
How to cite this URL:
Bay A, Yilmaz C, Yilmaz N, Oner AF. Vincristine induced cranial polyneuropathy. Indian J Pediatr [serial online] 2006 [cited 2006 Jul 14];73:531-533. Available from: http://www.ijppediatricsindia.org/article.asp?issn=0019-5456;year=2006;volume=73;issue=6;spage=531;epage=533;aulast=Bay
Vincristine is a vinca alkaloid used in combination with other agents in the treatment of solid tumors, lymphoma, and leukemia.[1] Severe vincristine toxicity is uncommon: in a detailed review, only 3.6% of the patients in POG 9201 had significant toxicity reported, with only 2.9% of patients having any alteration in therapy.[2] The dose limiting toxicity of vincristine is its neurotoxicity. The pathogenesis of neuropathy is explaned by vincristine causes structural changes in the microtubules of peripheral nerves and interferes with axoplasmic transport.[3] It manifests as loss of deep tendon reflexes, neurotic pain, paresthesias, and wrist and foot drop. Less frequently, cranial nerve palsies, transient cortical blindness, oculomotor nerve dysfunction, jaw pain, facial palsy, sensorineural hearing loss, and laryngeal nerve paresis have been attributed to vincristine.[3],[4]
We describe a 5-year-old girl who showed complete recovery of vincristine induced cranial polyneuropathy with pyridoxine and pyridostigmine treatment.
Case Report
A 5-year-old girl was diagnosed preB cell ALL (FAB L1 subtype). She received chemotherapy including prednisolone (60 mg/m 2), L-asparaginase (10.000 U/m 2), vincristine (1,5 mg/m 2), and daunorubicin (25 mg/m 2) with triple intrathecal therapy according to the previously described modified St. Jude total therapy studies XIII with minor modification including high-dose methylprednisolone.[5] Five days after the fourth dose of vincristine, she presented with bilateral ptosis [Figure - 1]. There were no previous clinical symptoms of neuropathy and no positive history for inherited neuropathies. Neurological examination revealed bilateral ptosis, and complete external opthalmoplegia with normal pupillary and corneal reflexes. The remaining physical findings were normal. Laboratory evaluation revealed the following values: hemoglobin, 8.5 g/dL; platelet count, 70 000/mm 3; white blood cell count, 2 600/mm 3 aspartate aminotransferase, 138 U/L; alanine aminotransferase, 81 U/L; lactate dehydrogenase, 914 U/L; triglyceride 212 mg/dl and total bilurubin 2.2 mg/dl. Cerebrospinal fluid examination and cranial MRI was normal. We would like to emphasize that the development of ptosis in the patient receiving a chemotherapy regimen including vincristine should raise the suspicion of toxic cranial neuropathy. She received 3.8 mg (6 mg/m 2) cumulative dose of vincristin before development of ptosis. She did not receive further doses of vincristin ptoziz düzelene kadar. A neuroprotective and neuroregenerative treatment attempt with pyridoxine (150 mg/m 2 p.o. BID) and pyridostigmine (3 mg/kg p.o. BID) was initiated. The bilateral ptosis markedly improved after 7 days of pyridoxine and pyridostigmine treatment and completely resolved after two weeks [Figure - 2]. The both agents were given for 3 weeks and were well-tolerated without any side effects. During the follow up of 2 months we did not observe residue or recurrence of the ptosis.
Discussion
Vincristine-induced neuropathy is usually mild, severe complications including partial or total paralysis was reported in rare cases.[3] Symptoms usually appear 2 to 19 weeks after the commencement of vincristine.[4] Vincristine neurotoxicity is more severe under the following circumstances: if more than the recommended maximum cumulative dose of 30 to 50 mg is given, if the patient is hypersensitive to this drug, if there is pre-existing liver dysfunction or a hereditary neuropathy, and if other drugs such as allopurinol, erythromycin, isoniazid, mitomycin C, phenytoin, and itraconazole are concomitantly used.[6] In our patient we did not use high dose vincristin and the other concominant accelerating drugs.
The definitive diagnosis of a drug-induced neuropathy depends on the exclusion of other etiologies that may produce a similar clinical picture. The following characteristics of the present case support our initial diagnosis of vincristine-induced neurotoxicity as the cause of ptosis: (1) the time course of ocular changes in relation to the therapeutic schedule with vincristine; (2) resolution of symptoms after pyridoxine and pyridostigmine therapy; (3) normal CSF findings (ie, no atypical cells); and (4) absence of other parenchymal brain lesions on MRIscan.
Several cases of severe neurotoxicity associated with vincristine use in patients with underlying and asymptomatic Charcot-Marie-Tooth syndrome have been reported.[2],[7] Our patient returned to a normal neurologic status in a brief period of time, which is not a typical feature of vincristine neurotoxicity complicated by hereditary motor and sensory neuropathy type 1, where recovery is slow and incomplete.
In animal studies pyridoxine has been demonstrated to induce some neuroprotection during intrathecal administration of lethal doses of vincristine.[8] Pyridostigmine or analogues have been used for enhancement of intestinal motility in patients with atonic bowel due to various causes, and reduction of gastrointestinal motility represents one of the major symptoms of vincristine-induced neuropathy.[9] Recently, Muller et al reported the full recovery of vincristine -associated bilateral ptosis after treatment with high dose pyridoxine and pyridostigmine in a 2 years old child.[10] We used the same treatment regimen in a 5 year old female with ALL who developed ptosis after chemotherapy treatment. This treatment was very well tolerated by a 5-year old girl with no documented side effects. We suggest that pyridoxine and pyridostigmine are safe and effective treatment options in vincristin-induced cranial neuropathy.
References
1. Quasthoff S, Hartung HP. Chemotherapy-induced peripheral neuropathy. J Neurol 2002; 249: 9-17.
2. Chauvenet AR, Shashi V, Selsky C, Morgan E, Kurtzberg J, Bell B Vincristine-induced neuropathy as the initial presentation of charcot-marie-tooth disease in acute lymphoblastic leukemia: a Pediatric Oncology Group study. J Pediatr Hematol Oncol 2003; 25 : 316-320.
3. Moudgil SS, Riggs JE. Fulminant peripheral neuropathy with severe quadriparesis associated with vincristine therapy. Ann Pharmacother 2000; 34 : 1136-1138.
4. Legha SS. Vincristine neurotoxicity. Pathophysiology and management. Med Toxicol 1986; 1 : 421-427.
5. Yetgin S, Tuncer MA, Cetin M et al. Benefit of high-dose methylprednisolone in comparison with conventional-dose prednisolone during remission induction therapy in childhood acute lymphoblastic leukemia for long-term follow-up. Leukemia 2003; 17 : 328-333.
6. Chan JD. Pharmacokinetic drug interactions of vinca alkaloids: summary of case reports. Pharmacotherapy 1998; 18 : 1304-1307.
7. Neumann Y, Toren A, Rechavi G et al. Vincristine treatment triggering the expression of asymptomatic Charcot-Marie-Tooth disease. Med Pediatr Oncol 1996; 26 : 280-283.
8. Jackson DV, Jr., Pope EK, McMahan RA et al. Clinical trial of pyridoxine to reduce vincristine neurotoxicity. J Neurooncol 1986; 4 : 37-41.
9. Battle WM, Snape WJ, Jr., Alavi A et al. Colonic dysfunction in Diabetes mellitus. Gastroenterology 1980; 79 : 1217-1221.
10. Muller L, Kramm CM, Tenenbaum T, Wessalowski R, Gobel U. Treatment of vincristine-induced bilateral ptosis with pyridoxine and pyridostigmine. Pediatr Blood Cancer 2004; 42 : 287-288.(Bay Ali, Yilmaz Cahide, Y)