High-Dose Intravenous Immunoglobulin to Treat Cerebellar Degeneration
High-Dose Intravenous Immunoglobulin to Treat Cerebellar Degeneration
This study will examine whether high-dose intravenous immunoglobulin (IVIG) is safe and
 effective for treating cerebellar ataxia-degeneration of the cerebellum, the part of the
 brain responsible for coordinating muscle movements and balance. The disease causes a slowly
 progressive impairment of speech and balance, with patients often developing slurred speech,
 tremor, clumsiness of the hands, and walking difficulties (ataxia). IVIG is derived from
 donated blood that has been purified, cleaned and processed into a form that can be infused.
 IVIG is an immune suppressant that is routinely used to treat other neurological conditions.

 Patients 18 years of age and older with hereditary (genetic) or sporadic (unknown cause)
 cerebellar degeneration may be eligible for this 5-month study. They must have evidence of an
 immune component to their condition, such as gluten sensitivity or antiganglioside
 antibodies. Candidates will be screened with a neurological examination, a review of medical
 records and possibly blood tests.

 Participants will be randomly assigned to receive infusions of either IVIG or placebo (an
 inactive substance) through an arm vein once a month for two months. The infusions will be
 given in the hospital in doses divided over 2 days, each lasting 6 to 10 hours. Before the
 infusions, patients will undergo ataxia assessments through tests of coordination and balance
 that may involve finger tapping, walking in a straight line, talking, and eye movements. When
 the treatment is finished, patients will be followed in the clinic once a month for 3 months
 for blood tests repeat ataxia assessments to evaluate the effects of treatment.
There is increasing evidence that there is an antibody mediated, autoimmune component in
 hereditary and sporadic cerebellar degeneration. The objective of this study is to show
 clinical improvement or stabilization in ataxia using treatment with intravenous
 immunoglobulin (IVIG) treatment. This study is a clinical, randomized, placebo-controlled
 trial of IVIG in adult patients with cerebellar ataxia. Patients will be selected from the
 motor control clinic based on a diagnosis of sporadic or hereditary cerebellar degeneration.
 Study drug (placebo versus active) will be given in an intravenous infusion over a 2-day
 period while the patient is hospitalized. This will be repeated monthly for 2 months.
 Efficacy measurement will include clinical ataxia rating scales, motor speed testing and
 clinical gait evaluation. These will be performed at baseline, during each hospitalization,
 and 1 month following final IVIG infusion. Main outcome measure will be difference from
 baseline in score on the NINDS ataxia rating scale 1 month following 2 treatments of 2 mg/kg
 IVIG (total 4 mg/kg).
INCLUSION CRITERIA:

 Adults over 18 with hereditary or sporadic cerebellar degeneration. Sporadic cerebellar
 degeneration may include the cerebellar predominant variant of Multiple System Atrophy
 (MSA-C). Hereditary ataxia is limited to the SCAs (spinocerebellar ataxias) or those
 patients with clear autosomal dominant ataxia. Patients must also have evidence for an
 immune component to their condition such as gluten-sensitivity or antiganglioside
 antibodies.

 EXCLUSION CRITERIA:

 Patients on the gluten-free diet. Those who wish to participate in this trial must be off
 the diet for a period of 3 months prior to the start of the study.

 Patients with Friedreich's ataxia. To date, this has not been associated with autoimmune
 phenomena. We would not expect this population to respond.

 Patients with other autosomal recessive and mitochondrial forms of ataxia, since
 autoimmunity has not been studied in this population.

 Patients with hypercoaguable disorders. This includes conditions like Protein C or S
 deficiency, underlying malignancy and/or paraproteinemia.

 Patient with acute renal insufficiency or patients on known nephrotoxic drugs.

 Patients with selective IgA deficiency

 Known paraneoplastic cerebellar degeneration.

 Cerebellar ataxia that is congenital, static and/or symptomatic (due to stroke, tumor,
 demyelinating or infectious).

 Women who are pregnant or lactating. Those of child-bearing age will be asked to use
 effective contraception for the duration of the study.

 Those patients who do not wish to use a product derived from human serum (for example,
 Jehovah's Witness).