Neurotoxicity of isolated limb perfusion with tumor necrosis factor

J Neurol Sci. 1998 Jun 11;158(1):1-4. doi: 10.1016/s0022-510x(98)00098-7.


Hyperthermic isolated limb perfusion (HILP) with tumor necrosis factor alpha (TNFalpha) is effective for advanced melanoma and sarcoma of the limbs. Ten patients undergoing HILP with TNFalpha were evaluated by neurological examinations, nerve conduction studies (NCS), sympathetic skin responses (SSR) and conventional and quantitative electromyography (EMG), performed before, 7 days and 6 weeks following HILP. Seven patients showed minimal clinical signs of peripheral nerve damage following HILP; in two the injury was evident electrophysiologically: 7 days following HILP five patients had paresthesias and/or hypoesthesia, one had a mild foot drop and one had autonomic disturbances in the affected limb. SSR was low in two patients in the affected limb, sensory nerve action potentials were not elicited in one, with normal motor NCS and EMG. At 6 weeks, four patients continued to have mild paresthesias and one had dysautonomia of the perfused limb. Sensory responses and SSR did not change, motor abnormalities were not found. These findings show that HILP with TNFalpha induces a mild, mainly sensory neuropathy in perfused limbs, not disturbing functionality and improving over time.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents, Alkylating / administration & dosage
  • Antineoplastic Agents, Alkylating / therapeutic use
  • Arm / innervation*
  • Autonomic Nervous System Diseases / chemically induced*
  • Chemotherapy, Cancer, Regional Perfusion
  • Combined Modality Therapy
  • Electromyography
  • Female
  • Humans
  • Hyperthermia, Induced
  • Immunologic Factors / administration & dosage
  • Immunologic Factors / adverse effects*
  • Immunologic Factors / pharmacology
  • Immunologic Factors / therapeutic use
  • Leg / innervation*
  • Male
  • Melanoma / secondary*
  • Melanoma / therapy
  • Melphalan / administration & dosage
  • Melphalan / therapeutic use
  • Middle Aged
  • Neural Conduction / drug effects
  • Paresthesia / chemically induced*
  • Peripheral Nervous System Diseases / chemically induced*
  • Prognosis
  • Reflex, Abnormal
  • Sarcoma, Kaposi / secondary*
  • Sarcoma, Kaposi / therapy
  • Soft Tissue Neoplasms / secondary*
  • Soft Tissue Neoplasms / therapy
  • Tumor Necrosis Factor-alpha / administration & dosage
  • Tumor Necrosis Factor-alpha / adverse effects*
  • Tumor Necrosis Factor-alpha / pharmacology
  • Tumor Necrosis Factor-alpha / therapeutic use


  • Antineoplastic Agents, Alkylating
  • Immunologic Factors
  • Tumor Necrosis Factor-alpha
  • Melphalan