eMedicine Specialties > Neurology > Neuro-oncology
Paraneoplastic Encephalomyelitis: Treatment & Medication
Updated: Jun 11, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
- Multimedia
Treatment
Medical Care
Timely diagnosis of paraneoplastic encephalomyelitis (PEM) is critical to allow for appropriate treatment of the underlying malignancy.13
- Immunosuppressive therapies are used frequently to treat PEM; however, no benefit has been documented.14
- Plasmapheresis may be instituted alone or in combination with other immunosuppressive therapies.
- As remission of neurologic sequelae occasionally has followed complete treatment of the tumor15 , efforts should be directed to the diagnosis and treatment of the associated cancer.
- Treatment of PEM includes physical therapy, symptomatic care, and prevention of medical complications.
Surgical Care
Surgical treatment options do not exist other than for the primary cancer.
Consultations
- Neurologist
- Oncologist
- Rehabilitation specialist
Diet
Specific dietary requirements do not exist, although aspiration precautions may be necessary in debilitated patients.
Activity
The presence of neurologic deficits and postural hypotension may necessitate supervision of activity or precautions to avoid falls.
Medication
Although no effective treatment is available, immunosuppressive therapies are frequently used.16 Immunosuppressive medications include corticosteroids, cyclophosphamide, and intravenous immunoglobulin (IVIG). Recent trials have included rituximab as a treatment for this condition.17 Anticonvulsants are used for seizure prophylaxis.
Corticosteroids
These agents modify autoimmune-mediated inflammation.
Methylprednisolone (Solu-Medrol, Medrol, Adlone, Depo-Medrol)
Has anti-inflammatory properties. Decreases inflammation by suppressing migration of polymorphonuclear leukocytes and reversing increased capillary permeability.
Initial PO daily dosage variable, with subsequent dose modification based on clinical response. Constant monitoring may be necessary to adjust for changes in clinical status and environmental stressors. After long-term therapy, taper drug gradually.
Adult
2-60 mg/d PO in 1-4 divided doses, followed by gradual reduction to lowest level that will maintain clinical response
Pediatric
Not established
Avoid concomitant cyclosporine; inducers of hepatic enzymes, such as phenobarbital, phenytoin, and rifampin, may require increased doses; troleandomycin and ketoconazole may diminish clearance; may have variable effects on antithrombotics, such as aspirin or warfarin
Documented hypersensitivity; systemic fungal infections
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Drug-induced secondary adrenocortical insufficiency may occur with abrupt discontinuation; corticosteroids have increased effects in patients with hypothyroidism or cirrhosis; corneal perforation may occur in setting of ocular herpes simplex infection; variable psychiatric manifestations may be induced; caution in patients with ulcerative colitis, diverticulitis, peptic ulcer disease, renal failure, hypertension, myasthenia gravis, osteoporosis, or Kaposi sarcoma; monitor growth and development of children
Prednisone (Deltasone, Meticorten, Orasone)
Has anti-inflammatory properties. May decrease inflammation by reversing increased capillary permeability and suppressing PMN activity.
Initial PO daily dosage variable, with subsequent dose modification based on clinical response. Constant monitoring may be necessary to adjust for changes in clinical status and environmental stressors. After long-term therapy, taper drug gradually.
Adult
5-60 mg/d PO qd or divided bid/qid; taper over 2 wk, as symptoms resolve
Pediatric
Not established
Estrogens may decrease clearance; concurrent digoxin may cause digitalis toxicity secondary to hypokalemia; phenobarbital, phenytoin, and rifampin may increase metabolism (consider increasing maintenance dose); monitor for hypokalemia with coadministration of diuretics
Documented hypersensitivity; viral infection, peptic ulcer disease, hepatic dysfunction, connective tissue infections, and fungal or tubercular skin infections; GI disease
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Drug-induced secondary adrenocortical insufficiency may occur with abrupt discontinuation; corticosteroids have increased effects in patients with hypothyroidism or cirrhosis; corneal perforation may occur in setting of ocular herpes simplex infection; variable psychiatric manifestations may be induced; caution in patients with ulcerative colitis, diverticulitis, peptic ulcer disease, renal failure, hypertension, myasthenia gravis, osteoporosis, or Kaposi sarcoma; monitor growth and development of children who are administered corticosteroids
Immunomodulators
They cause immunosuppressive reduction in inflammation-mediated neurologic injury.
Cyclophosphamide (Cytoxan, Neosar)
Has immunosuppressive properties. Chemically related to nitrogen mustards. As alkylating agent, mechanism of action of active metabolites may involve cross-linking of DNA, which may interfere with growth of normal and neoplastic cells.
PO/IV daily dosage recommendations have not been formulated for treatment of PEM. Modify dose based on clinical response or degree of leukopenia.
Adult
Administer per institutional protocol
Pediatric
Not established
Long-term administration of phenobarbital may alter effects; increases effects of succinylcholine chloride
Documented hypersensitivity; severely decreased bone marrow function
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Toxicity has been associated with leukopenia, thrombocytopenia, bone marrow infiltration, history of radiation, history of chemotherapy, hepatic dysfunction, and renal failure; regularly monitor hematologic parameters; may interfere with wound healing
Intravenous immunoglobulin (IVIG; Gamimune, Gammagard, Sandoglobulin, Gammar-P)
Neutralizes circulating antibodies through anti-idiotypic antibodies. Down-regulates proinflammatory cytokines, including IFN-gamma. Blocks Fc receptors on macrophages. Suppresses inducer T and B cells and augments suppressor T cells. Blocks complement cascade. May increase CSF IgG (10%).
IV dosage recommendations have not been formulated for treatment of PEM.
Adult
Administer per institutional protocol
Pediatric
Not established
Increases toxicity of live virus vaccine (MMR); do not administer within 3 months of vaccine
Documented hypersensitivity; isolated IgA deficiency
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Check serum IgA before IVIG (use IgA-depleted product, eg, Gammagard S/D); may increase serum viscosity and thromboembolic events; may increase risk of migraine attacks, aseptic meningitis (10%), urticaria, pruritus, or petechiae (2-30 d postinfusion)
Increases risk of renal tubular necrosis in elderly patients and in patients with diabetes, volume depletion, or preexisting kidney disease; lab changes associated with infusions include elevated antiviral or antibacterial antibody titers for 1 mo, 6-fold increase in ESR for 2-3 wk, and apparent hyponatremia
Anticonvulsants
These agents are used for treatment and prophylaxis of seizures.
Fosphenytoin (Cerebyx)
Diphosphate ester salt of phenytoin acts as water-soluble prodrug of phenytoin. Following administration, plasma esterases convert fosphenytoin to phosphate, formaldehyde, and phenytoin. Phenytoin in turn stabilizes neuronal membranes and decreases seizure activity.
To avoid need to perform molecular weight-based adjustments when converting between fosphenytoin and phenytoin sodium doses, express dose as phenytoin sodium equivalents (PE). Although can be administered IV and IM, IV route is route of choice and should be used in emergency situations.
Concomitant administration of an IV benzodiazepine usually necessary to control status epilepticus. Full antiepileptic effect of phenytoin, whether given as fosphenytoin or parenteral phenytoin, is not immediate.
Adult
15-20 mg/kg IV loading dose, followed by 300 mg IV q24h
Pediatric
Not established; use weight-adjusted dosage similar to that used in adults
Amiodarone, benzodiazepines, chloramphenicol, cimetidine, fluconazole, isoniazid, metronidazole, miconazole, phenylbutazone, succinimides, sulfonamides, omeprazole, phenacemide, disulfiram, ethanol (short-term ingestion), trimethoprim, and valproic acid may increase toxicity
Barbiturates, diazoxide, ethanol (long-term ingestion), rifampin, antacids, charcoal, carbamazepine, theophylline, and sucralfate may decrease effects
Decreases effects of acetaminophen, corticosteroids, dicumarol, disopyramide, doxycycline, estrogens, haloperidol, amiodarone, carbamazepine, cardiac glycosides, quinidine, theophylline, methadone, metyrapone, mexiletine, oral contraceptives, valproic acid
Documented hypersensitivity; sinus bradycardia; sinoatrial or third-degree AV block; Adams-Stokes syndrome
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Avoid rapid administration to reduce risk of hypotension and cardiac arrhythmias; monitor for blood dyscrasias with serial blood tests; discontinue use if skin rash appears and do not resume use if rash is exfoliative, bullous, or purpuric; use caution in patients with acute intermittent porphyria, diabetes, or hepatic dysfunction
More on Paraneoplastic Encephalomyelitis |
| Overview: Paraneoplastic Encephalomyelitis |
| Differential Diagnoses & Workup: Paraneoplastic Encephalomyelitis |
 Treatment & Medication: Paraneoplastic Encephalomyelitis |
| Follow-up: Paraneoplastic Encephalomyelitis |
| Multimedia: Paraneoplastic Encephalomyelitis |
| References |
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Further Reading
Keywords
anti-Hu syndrome, anti-Hu–associated paraneoplastic encephalomyelitis, paraneoplastic limbic encephalitis, paraneoplastic limbic encephalopathy, paraneoplastic brainstem encephalopathy, paraneoplastic myelopathy, subacute sensory neuronopathy, SSN, paraneoplastic ganglioradiculoneuritis, paraneoplastic sensory neuropathy, paraneoplastic encephalomyelitis, PEM, multifocal inflammatory CNS disorder
