Journal of Neurology

, Volume 234, Issue 1, pp 36–39 | Cite as

A controlled trial of isoniazid therapy for action tremor in multiple sclerosis

  • C. B. Bozek
  • L. F. Kastrukoff
  • J. M. Wright
  • T. L. Perry
  • T. A. Larsen
Original Investigations


Ten patients with clinically definite multiple sclerosis (MS) and action tremor were treated with isoniazid (INH) in a double-blind single crossover trial. The daily dose of INH administered during the 4-week treatment phase of the trial was determined by acetylator phenotype with slow acetylators receiving 12 mg/kg per day and rapid acetylators 20 mg/kg per day. Six of eight patients who completed the trial showed clinical improvement in the postural (alternating) tremor while on INH but the degree was minimal in all cases. Results of tremograms indicated that improvement also occurred in the intentional (synchronous) component of three patients while on INH, but this did not achieve statistical significance. Cerebrospinal fluid (CSF) levels of γ-aminobutyric acid (GABA) homocarnosine and ornithine were markedly elevated with INH therapy (providing evidence for substantial inhibition of GABA aminotransferase activity and increase in GABA in the CNS), but no correlation was found between the degree of GABA elevation in the CSF and the clinical response. Side effects were minimal and well tolerated. Although INH appears to have a limited therapeutic role, a trial is warranted in MS patients with postural tremor.

Key words

Action tremor Multiple sclerosis Isoniazid 


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  1. 1.
    Andrew CJ, Lance JW (1973) The comparison of tremors in normal, Parkinsonian and athetotic man. J Neurol Sci 19:53–61Google Scholar
  2. 2.
    Cerrea RME, Mettler FA (1955) Function of the primate brachium conjunctivum and related structures. J Comp Neurol 102:151–322Google Scholar
  3. 3.
    Cooper IS (1969) Involuntary movement disorders. Hoeber Medical Division, Harper and Rowe, New YorkGoogle Scholar
  4. 4.
    Fahn S (1976) Regional distribution studies of GABA and other putative neurotransmitters and their enzymes. In: Roberts E, Chase TN, Tower DB (eds) GABA in neuron system function. Raven New York, pp 169–186Google Scholar
  5. 5.
    Findley LF, Gresty MA (1980) Suppression of “rubral” tremor with levodopa. Br Med J 281:1043Google Scholar
  6. 6.
    Hallett M, Lindsey JW, Adelstein B, O'Riley P (1985) Controlled trial of isoniazid therapy for severe postural cerebellar tremor in multiple sclerosis. Neurology (Cleveland) 35:1374–1377Google Scholar
  7. 7.
    Huffman RD, Davis R (1977) Pharmacology of the brachium conjunctivum: Red nucleus synaptic system in the baboon. J Neurol Sci Res 3:175–192Google Scholar
  8. 8.
    Krayenbuhl H, Yasargil M (1962) Relief of intention tremor due to multiple sclerosis by sterotaxic thalomotomy. Confin Neurol 22:368–374Google Scholar
  9. 9.
    Kurtzke JF, Berlin L (1954) The effects of isoniazid on patients with multiple sclerosis. Am Rev Tuberc Pulm Dis 70:577–592Google Scholar
  10. 10.
    Kurtzke JF, Berlin L (1957) Isoniazid in treatment of multiple sclerosis. JAMA 163:172–174Google Scholar
  11. 11.
    McGeer EG, McGeer PL (1978) GABA containing neurons in schizophrenia, Huntington's chorea, and normal aging. In: GABA neurotransmitters. Alfred Benzon Symp 12:340–356Google Scholar
  12. 12.
    Morrow J, McDowell H, Ritchie C, Patterson V (1985) Isoniazid and action tremor in multiple sclerosis. J Neurol Neurosurg Psychiatry 48:282–283Google Scholar
  13. 13.
    Nieoullan LA, Dusticier N (1981) Increased glutamate decarboxylase activity in the red nucleus of the adult rat after cerebellar lesions. Brain Res 224:129–139Google Scholar
  14. 14.
    Ojemann GA, Ward AA (1982) Abnormal movement disorders. Neurol Surg 6:3852–3853Google Scholar
  15. 15.
    Perry TL, Stedman D, Hansen S (1968) A versatile lithium buffer elution system for single column automatic amino acid chromatography. J Chromatogr 38:460–466Google Scholar
  16. 16.
    Perry TL, Urquhart N, Hansen S, Kennedy J (1974) γ-aminobutyric acid: drug induced elevation in monkey brain. J Neurochem 23:443–445Google Scholar
  17. 17.
    Perry TL, Hansen S, Kennedy J (1975) CSF amino acids and plasma-CSF amino acid ratios in adults. J Neurochem 24:587–589Google Scholar
  18. 18.
    Perry TL, Kish SJ, Hansen S (1981) Elevation of brain GABA content by chronic low dosage adminstration of hydrazine, a metabolite of isoniazid. J Neurochem 37:32–39Google Scholar
  19. 19.
    Perry TL, Wright JM, Hansen S (1982) A double-blind clinical trial of isoniazid in Huntington disease. Neurology (NY) 32:354–358Google Scholar
  20. 20.
    Perry TL, Hansen S, Wall RA, Gauthier SG (1982) Human CSF GABA concentrations: revised downward for controls, but not decreased in Huntington's chorea. J Neurochem 38:766–773Google Scholar
  21. 21.
    Price-Evans DA (1969) An improved and simplified method of detecting the acetylator phenotype. J Med Genet 6:405–407Google Scholar
  22. 22.
    Sabra AF, Hallett M (1984) Action tremor with alternating activity in antagonist muscles. Neurology (NY) 34:151–156Google Scholar
  23. 23.
    Sabra AF, Hallett M, Sudarsky I, Mullally W (1982) Treatment of action tremor in multiple sclerosis with isoniazid. Neurology (NY) 32:912–913Google Scholar
  24. 24.
    Scheinberg L, Giesser BS (1984) INH in multiple sclerosis. Neurology (NY) 34:134Google Scholar
  25. 25.
    Schumacher GA, Beehe G, Kibler RF, Kurland LT, Kurtzke JF, McDowell F, Nagler B, Sibley WA, Tourtellote WW, Willum TL (1965) Problems of experimental trials of therapy in multiple sclerosis: report by the panel on evaluation of experimental trials of therapy in MS. Ann NY Acid Sci 122:552–568Google Scholar
  26. 26.
    Veterans Administration MS Study Group (1957) Isoniazid in treatment of multiple sclerosis. JAMA 163:168–172Google Scholar
  27. 27.
    Wright JM, Stokes EF, Sweeney VP (1982) Isoniazid-induced carbamazepine toxicity and vice versa. A double-blind interaction. N Engl T Med 307:1325–1327Google Scholar

Copyright information

© Springer-Verlag 1987

Authors and Affiliations

  • C. B. Bozek
    • 1
  • L. F. Kastrukoff
    • 1
  • J. M. Wright
    • 1
    • 2
  • T. L. Perry
    • 2
  • T. A. Larsen
    • 1
  1. 1.Department of Medicine, Acute Care Unit, Health Sciences Centre HospitalUniversity of British ColumbiaVancouverCanada
  2. 2.Department of Pharmacology and Therapeutics, Faculty of MedicineUniversity of British ColumbiaVancouverCanada

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