Sarcoidosis May Cause Neuropathy

Researchers from Chiba University in Japan have found that peripheral neuropathy can be a rare manifestation of sarcoidosis, which is a disease of unknown cause that leads to inflammation.

Normally, your immune system defends your body against foreign or harmful substances. These cells release chemicals that recruit other cells to isolate and destroy the harmful substance. Inflammation occurs during this process.

Once the harmful substance is destroyed, the cells and the inflammation go away, except in people who have sarcoidosis, where the inflammation doesn’t go away. In these cases some of the immune system cells cluster to form lumps called granulomas in various organs in your body and damage them.

In this study three patients with sarcoidosis presented with multiple mononeuropathy as the initial symptoms. Nerve conduction studies showed prominent multifocal conduction blocks in the nerve trunk.

In all three patients, corticosteroid treatment resulted in a dramatic clinical improvement associated with rapid resolution of conduction blocks. Subsequent electrodiagnostic findings suggested that demyelinative or ischemic-functional conduction block was responsible for their neuropathy.

(full article)

Mycophenolate mofetil as adjunctive therapy

Multifocal motor neuropathy (MMN) is an immune-mediated disorder characterized by slowly progressive asymmetrical limb weakness.

Immunoglobulins (IVIg) remains the primary, FDA-approved, means to treat the condition.

Anecdotal evidence suggests that immunosuppressive drugs as adjunctive therapy may be beneficial.

Safety and efficacy of mycophenolate mofetil (CellCept) as adjunctive therapy for MMN patients receiving IVIg maintenance treatment were evaluated in a randomized controlled trial.

MMN patients responding to IVIg treatment were eligible for randomization.

Muscle strength and functional status were assessed at monthly intervals for 1 year.

Three months after the start of CellCept or placebo treatment, IVIg doses were reduced step-wise, until a deterioration of functioning or decline in muscle strength could be observed.

An IVIg dose reduction of 50% during adjunctive treatment was defined as a primary endpoint.

Secondary outcome measures were improvement in muscle strength and functional status after 3 months and reduction of anti GM1-IgM titres after 12 months of CellCept treatment.

Twenty-eight patients were randomized, while one patient allocated to CellCept reached the primary endpoint of 50% IVIg dose reduction.

After 12 months IVIg reduction did not differ significantly between the two treatment groups.

Patients did not experience drug toxicity and none of the patients showed significant disease progression after 12 months.

Muscle strength and functional scores after 3 months and anti GM1-IgM titres after 12 months did not change.

Adjunctive treatment of MMN patients with CellCept at a dose of 1 g twice daily is safe but does not alter disease course or allow significant reduction of IVIg doses.

(full text)

After the study was published the FDA came out with an alert of a possible relationship between CellCept and a rare, but serious, neurological disease called multifocal leukoencephalopathy (PML). Other diseases associated with CellCept arePolyomavirus associated nephropathy (PVAN), cytomegalovirus (CMV) infections, reactivation of hepatitis B (HBV) or hepatitis C (HCV).

Multifocal Motor Neuropathy Review

Multifocal motor neuropathy (MMN) is an acquired immune-mediated neuropathy characterized by chronic or stepwise progressive asymmetrical limb weakness without sensory deficits. The upper extremities are more often affected than the lower extremities with distal paresis dominating over proximal paresis. Important diagnostic features are persistent multifocal partial conduction blocks (CBs) and the presence of high-titer anti-GM1 serum antibodies. Motor neuron disease, other chronic dysimmune neuropathies, such as chronic inflammatory demyelinating polyneuropathy and the Lewis-Sumner syndrome (MADSAM neuropathy), are important differential diagnoses. While corticosteroids and plasma exchange are largely ineffective, high-dose intravenous immunoglobulins are regarded as first-line treatment. In spite of significant success in elucidating the underlying disease mechanisms in MMN during the past few years, important pathophysiological issues and the optimum long-term therapy remain to be clarified. The present review summarizes the clinical picture and current pathophysiological concepts of MMN with a special focus on the molecular and electrophysiological basis of CBs and highlights established therapies as well as possible novel treatment options. Copyright © 2010 S. Karger AG, Basel.