| Considering IVIG therapy for your child's condition? |
| You can contact Dr. Kovacevic by e-mail and ask for his opinion on the applicability of IVIG treatment in your child's case. If you would prefer to meet with the Doctor you can call our offices and arrange an appointment. If you decide to make the appointment, please make sure that copies of your child's' pertinent medical records arrive to our offices at least 1 week in advance of the appointment. Dr. Kovacevic insists on examining the medical records beforehand, so that the meeting can be more efficient and fruitful. |
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| Intravenous Immunoglobulin Therapy in Pediatric Neuropsychiatric Disorders |
Dr. Kovacevic has had a vast experience in use of the IVIG (intravenous immune globulin) therapy for various medical conditions in children, including Guillain-Barre syndrome, Kawasaki syndrome, Opsoclonus -Myoclonus syndrome, Dermatomyositis, Juvenile Rheumatoid Arthritis, PANDAS & PITAND, post-infectious Encephalitis, ADEM, Autism, etc. While extremely successful in Guillain-Barre, Kawasaki and Dermatomyositis, IVIG therapy has also shown a great deal of promise in PANDAS and PITAND syndromes, post-infectious Encephalitis and ADEM (into this group belongs a vaccine induced brain damage), and Opsoclonus-Myoclonus (without Neuroblastoma). The experience with the use of IVIG in Autism has been less satisfactory. In carefully chosen cases however, a significant benefits can be achieved. Dr. Kovacevic uses Gamunex from Bayer.
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| For more information on IVIG therapy in PANDAS please refer to our page with PANDAS clinical cases. |
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Recent scientific evidences are pointing out that an infectious agent(s) may play an important role in the pathophysiology of certain neuropsychiatric disorders in children 1,11,17,19,20 . Group A beta-hemolytic Streptococcus (GABS), and (possibly) other microorganisms (bacteria and viruses) have been implicated as causative agents in the ethiology of at least some cases of Obsessive Compulsive Disorders in children1,8,19,20, tic disorders (including Tourette's)1,18,19,20 , Autistic Spectrum Disorders10 and Anorexia Nervosa17. Presumed pathophysiological mechanisms are likely based on neurotropic auto immune antibody injury to the neurons20.
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| If your child has been diagnosed with PANDAS or PITAND syndrome and have questions about and/or treatment for these conditions please review our PANDAS clinical cases page! |
| Intravenous immune globulin (IVIG) has exhibited clear benefits in a number of auto immune diseases 4,6,7,9,13,15,18,21 and there is an accumulating body of evidence that these benefits might extend into the area of pediatric neuropsychiatric disorders as well1,3,8,10,14. The true mechanisms of IVIG action in neuropsychiatric disorders are still poorly understood, however an interference with auto immune antibody binding sites and/or inhibition of auto immune antibody production has been suggested 3,4,21.One of the more exciting possibilities is the recent speculation that IVIG can also aid in the recovery of already damaged neurons5,16. |
| IVIG treatment has been widely used and its safety has been proven13. Minor, self-limiting reactions to IVIG (fever, muscle aches and pains, headaches, nausea and vomiting, dizziness, tachycardia) have been reported in less than 5% of patients. Rarely (less than 1 in 1,000 patients) severe allergic reactions have occurred, but if handled properly no resulting harm has been reported. |
| Certain other rare complications have been also reported in literature and one should be aware of them: aseptic meningitis, renal toxicity (acute renal failure), vascular thrombosis and hyperviscosity syndrome. It appears however, that these complications may be directly related to the brand of IVIG used. Products where sugars (sucrose in particular) have been used as stabilizing agents may increase the likehood of some of these rare complications. |
| Conditions/disorders where IVIG treatment has shown promising results: Kawasaki syndrome(1), Guillain-Barre syndrome(1), Dermatomyositis(2), PANDAS(3), PITAND(3), Opsoclonus-Myoclonus(3) (without Neuroblastoma), neurologic sequel of a viral encephalitis(3) (particularly Herpes simplex virus, and enteroviruses, particularly Enterovirus 71), post-infectious encephalitis(3) (acute disseminated encephalitis - ADEM; can follow certain viral infections and/or the administration of certain viral vaccines), intractable (refractory) seizures(4) and in certain carefully chosen cases of Autism(5) and Anorexia Nervosa(5). |
| 1 Use of IVIG in these condition has been approved. It is covered by most health insurance companies. |
| 2 Use of IVIG in these condition has been reported successful. It has been accepted as an alternative treatment. Treatment coverage by the insurance companies may vary. |
| 3 Variable successes of IVIG treatment have been reported in these conditions and its use has been controversial. Most of the insurance companies will NOT pay for the treatment. |
4 Use of IVIG in intractable seizures has had variable success, and it has not been widely accepted.
| *Vagal nerve stimulation may be an alternative in patients with refractory seizures; recent studies have shown very encouraging results. |
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| 5 Use of IVIG in Autistic Spectrum Disorders and certain cases of Anorexia Nervosa is highly controversial and considered experimental. (Please, refer to the following information elsewhere!) |
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| Recent studies have found IVIG therapy beneficial in STEVENS-JOHNSON SYNDROME and TOXIC EPIDERMAL NECROLYSIS, two of the most severe skin reactions known in children. |
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| Another potential benefit of IVIG treatment has been reported from Israel, and may be the most important one to date: large animal studies as well as limited studies on patients with cancer are indicating that treatment with IVIG significantly reduces metastatic spread of certain cancers, particularly melanoma, carcinoma and sarcoma in these patients. Possibility of IVIG as an adjunct therapy in Neuroblastoma and Nesidioblastosis appears a tempting prospect. |
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| Treatment with IVIG (Intravenous Immunoglobulin) in neuropsychiatric disorders in children is still not considered a standard treatment for these diseases and might not be covered by some health insurance carriers. It is costly and there are no guarantees that it will be successful in any particular patient. Even if the desired effect has been achieved, it is still unknown how long would the benefit last and when and if additional treatment(s) might be needed. |
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Criteria for Admission to Treatment for PANDAS and PITAND syndromes
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PANDAS
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(1) At some time in his or her life, the patient must have met diagnostic criteria (DSM IV) for one of the following neuropsychiatric disorders: Obsessive Compulsive Disorder, Tic Disorder (including Tourette's), Anxiety disorder (especialy Separation anxiety disorder), Anorexia nervosa (see important details here!).
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(2) Pediatric onset: symptoms of the disorder first become evident between 18 months of age and the beginning of puberty.
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(3) The onset of clinically significant symptoms must be sudden (with or without a sub clinical prodrome), and/or there must be a pattern of sudden, recurrent, clinically significant symptom exacerbation and remissions ("wax and waning pattern"). Onset of a specific episode typically can be assigned to a particular day or week, at which time symptoms seem to "explode" in severity, and they are frequently associated with an infectious episode.
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(4) There must be evidence of an antecedent or concomitant infection. Such evidence might include a positive throat culture, positive streptococcal serologic findings (e.g. anti-streptolysin O or anti-streptococcal DNAse B), or a history of illness (e.g. pharyngitis, sinusitis, infection with Epstein-Barr virus, influenza, ?recurrent otitis media), and possibly recent exposure to certain childhood vaccinations.
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(5) Presence of auto-immune antibodies (anticardiolipin, antineuronal, antibody/antigen complexes, etc.)
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(6) During the exacerbation, the majority of patients will have an abnormal neuropsychiatric examination, frequently with hyperactivity and adventitious movements ("choreiform" movements), impaired fine motor skills and decrease in comprehension and learning abilities (especially math).
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(7) Measurable clinical improvement following "Steroid Burst".
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PITAND
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(1) Current presence of symptoms (DSM IV) of Obsessive Compulsive Disorder, Tic Disorder (including Tourette's), and Anorexia Nervosa*.
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(2) Symptom onset between 18 months of age and puberty.
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(3) Episodic course of symptom severity characterized by the abrupt onset of symptoms and/or frequent, dramatic symptom exacerbation.
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(4) Symptom exacerbation associated with GABS infection.
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(5) Presence of abnormal neuropsychiatric examination, including motor hyperactivity, adventitious movements, tics, etc.
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(6) Measurable clinical improvement following "Steroid Burst".
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| DISQUALIFYING FACTORS (absolute): Presence of symptoms before 1 year of age. |
| DISQUALIFYING FACTORS (relative): Confirmed Dg. of Autism and/or Autistic Spectrum Disorder in sibling(s). |
| Modified "Allen criteria" (from Albert J. Allen Group A Streptococcal Infections and Childhood Neuropsychiatric Disorders CNS Drugs Oct. 1997 8(4) 267-275 |
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Criteria for Admission to Treatment for ADEM
| POST - INFECTIOUS ENCEPHALITIS (ADEM): |
| (1) Patient's history compatible with Acute Disseminated Encephalitis (symptoms appearing 2-3 weeks following a non-specific upper respiratory infection caused by virus or certain bacterial agents (Mycoplasma pneumoniae), MMR or influenza vaccination. |
| (2) Exclusion of viral encephalitis (by laboratory, and/or clinically). |
| (3) Presence of characteristic asymmetrical, bilateral hyperintense lesions of the same age in the white matter and deep gray matter (T2-weighted or FLAIR images) on MRI of the brain. |
| (4) Significant multifocal neurologic abnormalities. |
| (5) Steroid therapy failure |
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