eMedicine Specialties > Neurology > Neurological Infections
Tropical Myeloneuropathies: Treatment & Medication
Updated: Jan 11, 2007
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
- Multimedia
Treatment
Medical Care
The mainstay of treatment is symptomatic. No standard treatment is available for TAN or HAM/TSP.
- HAM/TSP: A study of 131 patients reported that oral methylprednisolone produced excellent to moderate responses in 69.5% of patients (Nakagawa, 1996).
- Symptomatic treatment is similar to that used in primary lateral sclerosis (please see article Primary Lateral Sclerosis for further details). Drugs that can be used include baclofen, tizanidine, and benzodiazepines. Physical therapy is used commonly in combination.
- Patients with HAM/TSP or TAN sometimes report neuropathic pain. Useful drugs include antiepileptics (eg, carbamazepine, phenytoin, gabapentin, topiramate), baclofen, and tricyclic antidepressants. The dosages used usually are well bellow those used in the treatment of epilepsy. None of these drugs are approved by the FDA for this purpose.
- Controlled trials of antiviral agents (eg, zidovudine) in HAM/TSP are under review.
Consultations
Infectious disease specialist
Diet
TAN: Supplementation with multivitamins is recommended, but in most cases only minor improvement occurs. In areas where cassava flour is used, following standard cassava processing measures is imperative.
Medication
HAM/TSP
A multicenter, randomized, double-blind study in 48 patients indicated that treatment with subcutaneous interferon alfa (Roferon) 3 million U (MU) twice a week was effective in more than 66.7% (Izumo, 1996). In another study, 32 patients were treated with interferon alfa; 20 patients showed a fair-to-excellent response in motor function. The effect was sustained, however, for only 1-3 months after the last injection (Nakagawa, 1996).
An open-label study showed that pentoxifylline 300 mg PO once a day induced clinical improvement in 14 of 15 patients. The authors postulated that the effect probably was due to TNF-alpha suppression (Shirabe, 1997). In a recent open-label trial, 12 patients with HAM/TSP were treated with doses of interferon beta-1a of up to 60 µg twice weekly. During the trial, the therapy reduced the HTLV-1 tax messenger RNA load, but the HTLV-1 proviral DNA load remained unchanged. Some measures of motor function were improved, and no significant clinical progression occurred during therapy (Oh, 2005).
Interferons
These agents are naturally produced proteins with antiviral, antitumor, and immunomodulatory actions.
Interferon alfa-2a recombinant (Roferon-A)
Highly purified protein containing 165 amino acids, has approximate molecular weight of 19,000 Daltons. Mechanism of action not clearly understood; however, modulation of host immune response may play important role.
Adult
3 MU SC twice/wk
Pediatric
Not established
Theophylline may increase toxicity by reducing clearance; cimetidine may increase antitumor effects; zidovudine and vinblastine may increase toxicity
Documented hypersensitivity; avoid in patients who have anaphylactic sensitivity to mouse IgG, egg protein, or neomycin; autoimmune hepatitis
Pregnancy
C - Safety for use during pregnancy has not been established.
Precautions
Administer under guidance of qualified physician
Depression and suicidal behavior, including suicidal ideation, suicidal attempts, and suicides have been reported in association with treatment with alfa interferons, including Roferon-A
Adverse CNS reactions reported in number of patients, including decreased mental status, dizziness, impaired memory, agitation, manic behavior, and psychotic reactions; more severe obtundation and coma have been observed, rarely; most of these abnormalities were mild and reversible within few d to 3 wk on dose reduction or discontinuation of therapy; careful periodic neuropsychiatric monitoring of all patients recommended
Should be used with caution in patients with severe preexisting cardiac disease, severe renal or hepatic disease, seizure disorders, and/or compromised CNS function; caution in cardiac disease or any history of cardiac illness; acute, self-limited toxic effects (ie, fever, chills) frequently associated with Roferon-A; may exacerbate preexisting cardiac conditions; rarely, myocardial infarction occurred in patients receiving Roferon-A; cases of cardiomyopathy observed on rare occasions
Patients with history of autoimmune hepatitis or autoimmune disease and patients who are immunosuppressed transplant recipients should not be treated with Roferon-A; controlled studies of Roferon-A therapy in patients with advanced cirrhosis and/or decompensated liver disease have not been performed; in chronic hepatitis C, initiation of interferon alfa therapy, including Roferon-A, reported to cause transient liver abnormalities, which in patients with poorly compensated liver disease can result in increased ascites, hepatic failure, or death
Leukopenia and elevation of hepatic enzymes may occur but rarely dose limiting; thrombocytopenia occurred less frequently; proteinuria and increased cells in urinary sediment also seen infrequently; dose-limiting hepatic or renal toxic effects unusual; infrequently, severe renal toxic effects, sometimes requiring renal dialysis, reported with interferon alfa therapy alone or in combination with interleukin (IL)-2
Infrequently, severe or fatal GI hemorrhage reported in association with interferon alfa therapy
Caution in myelosuppression or when Roferon-A used in combination with other agents known to cause myelosuppression; synergistic toxicity has been observed when Roferon-A administered in combination with AZT; effects of Roferon-A when combined with other drugs used in treatment of AIDS-related disease not known
Hyperglycemia observed rarely in patients treated with Roferon-A; symptomatic patients should have their blood glucose measured and monitored; patients with diabetes mellitus may require adjustment of their antidiabetic regimen
Roferon-A should not be used for treatment of visceral AIDS-related Kaposi sarcoma associated with rapidly progressive or life-threatening disease
Injectable solutions contain benzyl alcohol and should not be used by patients with known allergy to benzyl alcohol; not indicated for use in neonates or infants and should not be used by patients in that age group; rare reports of death in neonates and infants associated with excessive exposure to benzyl alcohol; reports of permanent neuropsychiatric deficits and multiple system organ failure associated with benzyl alcohol in neonates and infants; amount of benzyl alcohol at which toxicity or adverse effects may occur in neonates or infants not known
Generally, in all instances in which use of Roferon-A considered for chemotherapy, physician must evaluate need and usefulness of drug against risk of adverse reactions; most adverse reactions are reversible, if detected early; if severe reactions occur, drug should be reduced in dosage or discontinued and appropriate corrective measures taken according to clinical judgment of physician; Roferon-A therapy should be reinstituted with caution and with adequate consideration of further need for drug and alertness to possible recurrence of toxicity
Minimum effective doses of Roferon-A for treatment of hairy cell leukemia, AIDS-related Kaposi sarcoma, and chronic myelogenous leukemia have not been established
Variations in dosage and adverse reactions exist among different brands of interferon (do not use different brands of interferon in single treatment regimen)
Rare cases of autoimmune diseases, including thrombocytopenia, vasculitis, Raynaud phenomenon, rheumatoid arthritis, lupus erythematosus, and rhabdomyolysis observed in patients treated with alfa interferons; any patient developing autoimmune disorder during treatment should be monitored closely and, if appropriate, treatment discontinued
Information for patient: Patients should be cautioned not to change brands of interferon without medical consultation, as change in dosage may result; patients should be informed regarding potential benefits and risks attendant to use of Roferon-A; if home use determined to be desirable, instructions on appropriate use should be given, including review of contents of enclosed patient information sheet; patients should be well hydrated, especially during initial stages of treatment
Patients should be instructed thoroughly in importance of proper disposal procedures and cautioned against reusing syringes and needles; if home use prescribed, puncture-resistant container for disposal of used syringes and needles should be supplied to patient; full container should be disposed of according to directions provided by physician
Patients receiving high-dose interferon alfa should be cautioned against performing tasks that require complete mental alertness, such as operating machinery or driving a motor vehicle; they should be informed that depression and suicidal ideation may be adverse effects of treatment and should be advised to report these effects immediately to prescribing physician
CBC count with differential platelet counts and clinical chemistry tests should be performed before initiation of Roferon-A therapy and at appropriate periods during therapy; since responses of hairy cell leukemia, AIDS-related Kaposi sarcoma, chronic hepatitis C, and chronic myelogenous leukemia generally are not observed for 1-3 mo after initiation of treatment, very careful monitoring for severe depression of blood cell counts is warranted during initial phase of treatment
Patients who have preexisting cardiac abnormalities and/or are in advanced stages of cancer should have ECGs taken before and during course of treatment
For patients being treated for chronic hepatitis C, serum alanine aminotransferase (ALT) should be evaluated before initiating therapy to establish baselines and repeated at week 2 and monthly thereafter following initiation of therapy for monitoring clinical response; because patients with neutrophil count <1500/µL, platelet count <75,000/µL, hemoglobin <10 g/dL, and creatinine >1.5 mg/dL were excluded from several major studies in chronic hepatitis C, patients with these laboratory abnormalities should be monitored carefully if treated with Roferon-A
Patients with preexisting thyroid abnormalities may be treated if normal TSH levels can be maintained by medication; testing of TSH levels in these patients is recommended at baseline and every 3 mo following initiation of therapy
Interferon beta-1a (Avonex, Rebif)
For treatment of relapsing remitting MS. Avonex has also gained approval for treating patients with a first MS attack if brain MRI shows abnormalities characteristic of MS. Believed to act via ability to counteract cell surface expression of proinflammatory or pro-adhesion molecules on immune cells, among other effects. More studies needed to fully understand mechanisms of action. Only differs from interferon beta-1b in that it has amino acid sequence identical to that of natural compound and is glycosylated. Presence of glycosylation may lead to structural stability and presumably to higher biological potency.
Interferons act through common receptor that activates Jak/Stat pathway of signal transduction molecules, which, in turn, lead to activation of interferon-responsive genes. Interferon beta may decrease expression of B7-1 (a proinflammatory molecule) on surface of immune cells and increase levels of TGF-beta (anti-inflammatory) in circulation of MS patients. Interferon beta-1a is most convenient ABC drug to administer due to weekly schedule.
Adult
Avonex: 30 mcg IM qwk
Rebif: 44 mcg SC 3 times/wk
Pediatric
Not established
Hematologic abnormalities including anemia, thrombocytopenia, and development of agranulocytopenia may occur when administered concomitantly with ACE inhibitors; may increase anticoagulant effects of warfarin; may increase toxicity of zidovudine
Documented hypersensitivity; liver dysfunction; severe leucopenia; thrombocytopenia; lactation
Pregnancy
D - Unsafe in pregnancy
Precautions
Caution in preexisting seizure disorder; cases of exacerbation of thyroid dysfunction have been described; caution when using interferon beta-1a in patients with uncontrolled thyroid dysfunction; besides a flu-like illness, patients may experience injection-site skin reactions; interferons are abortifacient; data on teratogenicity are limited; extreme caution in patients with severe depression, depression and suicide have been reported with increased frequency in patients receiving interferon products (including interferon beta-1a); monitor for hepatic toxicity
Blood viscosity reducer agents
These agents decrease the viscosity of blood.
Pentoxifylline (Trental)
May alter rheology of red blood cells, which, in turn, reduces blood viscosity
Adult
300 mg PO qd
Pediatric
Not established
Cimetidine or theophylline increases effect/toxic potential; increases effect of antihypertensives
Documented hypersensitivity; cerebral and/or retinal hemorrhage
Pregnancy
C - Safety for use during pregnancy has not been established.
Precautions
Caution in renal impairment; periodic blood pressure monitoring recommended for patients receiving concomitant antihypertensive therapy
More on Tropical Myeloneuropathies |
| Overview: Tropical Myeloneuropathies |
| Differential Diagnoses & Workup: Tropical Myeloneuropathies |
 Treatment & Medication: Tropical Myeloneuropathies |
| Follow-up: Tropical Myeloneuropathies |
| Multimedia: Tropical Myeloneuropathies |
| References |
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Further Reading
Keywords
tropical myeloneuropathy, tropical ataxic neuropathy, TAN, cassava, mantakassa, tropical spastic paraparesis, TSP, HTLV-1–associated myelopathy, HAM, upper motor neuron syndrome, sensory neuropathy
