Spinal Care, Neurology, Spinal Medical Advice and Information.
Chronic Inflammatory Demyelinating Polyneuropathy
Chronic inflammatory demyelinating polyneuropathy (CIDP) is a sporadic acquired disorder which may mimic an inherited neuropathy in childhood. In fact, the commonest chronic neuropathy seen in children is an hereditary motor and sensory neuropathy (HMSN) type I. Evidence of familial involvement is perhaps the single most important characteristic in distinguishing hereditary from acquired disorders in children. It is important to recognize the acquired CIDP since it is potentially a treatable disease and its diagnosis may be suggested by clinical, electrophysiologic and nerve biopsy features.
Chronic inflammatory demyelinating polyneuropathy (CIDP) is distinguished from the more common acute demyelinating neuropathy, the Guillain-Barre syndrome (GBS), chiefly by clinical course and prognosis. On the one hand, both disorders have similar clinical features, and both share the CSF albuminocytological dissociation and the pathological abnormalities of multi- focal inflammatory segmental demyelination with associated nerve conduction features reflecting demyelination. An autoimmune basis is suspected for both CIDP and GBS.
On the other hand, CIDP has a more protracted clinical course, is rarely associated with preceding infections in children and responds to corticosteroid therapy. In addition, CIDP has an association with HLA antigens as well as an association with the M-phenotype of alpha-one antitrypsin deficiency.
The clinical course can follow several patterns. The onset is usually gradual but there was around 15% rapid rate of onset in a series of 92 patients. It also showed that 65% have a relapsing course compared to 35% with progressive or monophasic course. There was a significantly earlier age of onset in patients with relapsing disease, a finding similar to that in multiple sclerosis. In fact, some authors have suggested that CIDP syndrome may be the peripheral nervous system counterpart of multiple sclerosis, another presumed autoimmune disorder.
The disease is seen in all age groups including the first year of life. In adults there may be a history of preceding infection, immunization, or injection of foreign material within one month before the onset of the symptoms. However, this is not usually the case in children. The majority of patients have symmetrical motor and sensory involvement, although occasionally cases with predominantly motor or predominantly sensory involvement may be seen. Proximal limb weakness is almost as severe as distal limb weakness, and the upper and lower extremities are equally affected but muscle wasting is rarely pronounced.
These signs provide helpful clinical clues to separate these patients from those with axonal neuropathies. Deep tendon reflexes are invariably depressed or absent at some stage of the disease. Sensory symptoms of stocking glove distribution described as numbness, asleep or tingling sensation implicating large fiber involvement occur frequently, but pain is much less common. Additional findings, listed in decreasing order of frequency, are postural tremor of the upper extremities, palpable thickening of peripheral nerve trunks, papilledema and bulbar and facial weakness. Autonomic dysfunction is rare.
Some patients may present with predominantly multi- focal motor signs masquerading as motor neuron disease. Electrophysiological studies demonstrating multi- focal conduction block confined to motor axons distinguish this acquired, demyelinating, multifocal motor neuropathy from motor neuron disease. The latter may be associated with high serum antibody titers to gangliosides and has been reported to respond to immunosuppression with cyclophosphamide. A CIDP-like syndrome may develop in cases of inherited neuropathy. These patients typically have a positive family history of affected kin, and have bony abnormalities such as pes cavus and hammer toes since an early age, but develop subacute deterioration with proximal muscle weakness and raised CSF protein. The newly acquired symptoms respond to corticosteroid therapy, hence the term prednisone-responsive hereditary motor and sensory neuropathy.
CIDP must be distinguished from hereditary demyelinating neuropathies such as the hypertrophic form of peroneal atrophy, Dejerine-Sottas disease, Refsum's disease, and the neuropathies associated with leukodystrophies, and from acquired demyelinating polyneuropathies linked with systemic disorders (diabetes mellitus, lymphoproliferative disorders, ulcerative colitis, uremia, SLE). However, most of the systemic disorders are rarely implicated in childhood. CIDP may also be associated with HIV infection.
The pattern of neuroconduction changes strongly suggests the diagnosis. This includes slowing of motor conduction velocities below 70% of normal. In CIDP the degree of slowing varies in different segments of the same nerve and in equivalent segments of different nerves in the same limb. This characteristic allows distinction between CIDP and inherited chronic demyelinating disorders since the latter shows uniform slowing of nerve conduction. CSF protein in excess of 45mg/dl is found in most cases, and levels above 100mg/dl are common. CSF pleocytosis is rare except in HIV-associated CIDP. A single monoclonal IgG band on agar gel electrophoresis and elevated myelin basic protein level may be detected in CSF and supports the diagnosis when present.
The sural nerve biopsy reveals segmental demyelinating and remyelination. The mononuclear infiltrate and macrophage-mediated demyelination are helpful findings. Onion bulb formations, a sign of repeated episodes of segmental demyelination and remyelination, depends on chronicity. In older children glue sniffing may produce the clinical features of CIDP and slow nerve conduction, however, nerve biopsy is usually diagnostic. Whether or not a serum from a patient with CIDP contains autoantibodies is still under debate.
Steroids are beneficial in CIDP, the prednisone dose is usually 0.5-1mg/kg/day. A favorable response is usually seen within 4 weeks. Patients in whom no response is seen, plasmapheresis has been proven to be efficient. However, recently high doses intravenous immunoglobulin have been shown to be effective in the management of CIDP. Clinical improvement was often dramatic and there were no reported major adverse reactions to the infusions.
Finally, the prognosis of CIDP is worse than GBS, but still appears to be somehow favorable in childhood. In one series, ten patients presented in childhood, eight were followed for an average of 10 years, and 7 had no disability, one case had minor disability only. Three of these cases experienced relapses in adult life.