Definition and Natural History
Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an acquired peripheral nerve disorder of presumed autoimmune etiology. Specific guidelines for the diagnosis and the natural history have been carefully set out, separating CIDP from the acute inflammatory demyelinating polyneuropathy, the Guillain-Barré Syndrome (GBS). Both conditions lead to fairly symmetrical weakness or flaccid limb paralyses, attenuation or loss of deep tendon reflexes altered sensation and parasthesias. Autonomic dysfunction and pain, both very frequent in GBS, are distinctly less common in CIDP and patients rarely require ventilatory support. The two conditions differ primarily in time course of evolution and reversal of clinical signs. In CIDP, motor and sensory deficits develop insidiously over weeks to months (an arbitrarily defined minimum of 8 weeks), leading eventually to significant disabilities. The occasional CIDP patient may present acutely as in GBS, but is shown subsequently to follow a progressive or relapsing course. This is particularly true for children, in whom the onset of symptoms is often more precipitous.

At presentation, proximal and distal weakness predominate, but objective sensory loss with gait ataxia and impaired dexterity also contribute significantly to the disability. In rare instances (<5%), the clinical presentation is purely sensory. Such patients have prominent sensory signs, gait ataxia, and often large amplitude action tremors but no weakness. Yet electrophysiological studies disclose typical findings of demyelination, not only in sensory but also in motor nerves. Idiopathic CIDP has also been differentiated from variant forms of chronic demyelinating neuropathies, occurring in association with monoclonal gammopathy of undetermined significance - CIDP-MGUS. The latter appear distinct, both in regards their natural history and their response to therapy CIDP-MGUS tends to follow a slowly progressive course, is seen primarily in older individuals (predominantly males) and leads to more pronounced sensory as opposed to motor deficits.

Thus the clinical presentation of CIDP encompasses a group of related but distinct disorders that differ not only in some of the clinical aspects but, more importantly, that appear to respond variably to the immunomodulatory therapies. A precise definition of the diagnosis is required prior to the formulation of a treatment plan.

Immunomodulatory Therapies
CIDP is considered an autoimmune disorder, caused by aberrant cellular and humoral immune responses. Treatments are aimed at modulating the abnormal immune responses and suppressing ongoing disease activity. This may be achieved by a variety of treatment modalities which are often prescribed individually or in combination. The options include infusions of immunoglobulin-G (IvIg), therapeutic plasma exchange (PE), corticosteroids or cytotoxic drugs such as Cyclophosphamide or Cyclosporin. Therapeutic efficacy for these various treatments has been confirmed in several randomized and controlled trials. There are no clear guidelines regarding the choice of the initial therapy. Moreover, responses in individual patients may vary and they cannot be clearly predicted. Failure to respond to one treatment does not preclude benefit from one of the other options. It is therefore, important to individualize the treatment plan for each patient. Choice of treatments may be dictated by medical circumstances and cost.

It is the collective experience that there are “responders'” and ''non-responders'' to IvIg; on the whole, benefit is seen in approximately two-thirds of patients. Predictors of a favorable response have been identified as: disease duration of < one year; ongoing disease progression; equal weakness of arms and legs; areflexia and slowing of motor conduction velocities of the median nerve. They identify patients with an actively ongoing demyelinating neuropathy with predominant motor deficits. The chance for improvement with IvIg was estimated at >90% if all five factors were present. Patients with sensory forms of CIDP are less likely to respond to long, but a trial assessment is warranted. Benefit or failure thereof, can be established in most circumstances with a single five-day course of IvIg infusions (0.4 gm/kg. body weight per day). Improvement, if it occurs, begins promptly it needs to be objectivity at defined time points (best weekly) with a set of measurements that are employed at baseline and in follow-up assessments. In relapsing midi benefit from IvIg is usually temporal lasting a median of 6 weeks (range 3 to 22 weeks). Regularly timed IvIg pulse treatments (given as single-day infusions, lgm/kg. body weight), combined with low-dose, alternate-day Prednisone (25 mg. q.2.days) may lead to long-term stabilization. Comparative studies indicate that IvIg and plasma exchange treatments confer equal short-term benefit. There are, however, IvIg ''non-responders'' who will benefit from PE. Substantial improvement with PE was documented in 80% of CIDP patients with either chronic progressive or relapsing disease. Improvement usually begins within days of starting PE; benefit, however, may only be temporary Prolonged PE treatments and a concurrent prescription of Prednisone or Cyclophosphamide may be required for stabilization. It is important to keep in mind that PE treatments can be followed by so-called “rebound relapse.” Corticosteroids have been the mainstay of treatment for CIDP. Retrospective analyses document improvement in 65 to 95% of CIDP patients. To achieve this benefit, high-dose Prednisone has to be prescribed for a minimum of six months (initial dose 1 mg/kg. body weight/day for 6 to 8 weeks, subsequent tapering by 10 mg/month and change to alternate-day dosing). First signs of improvement were seen at mean 1.9 months and maximum benefit was reached only after a mean 6.6 months. Patients may relapse when steroids are tapered or discontinued. The required prolonged prescription of steroids may lead to the well-know and sometimes hazardous side effects. These can be avoided by monthly pulse treatments with intravenous Methylprednisolone, 500 mg. on 3 consecutive days, which can be equally effective. For some cases, other immunosuppressive drugs (such as Cyclophosphamide or Cyclosporine) will have to be added to achieve long-lasting stabilization and remission.

With a judicious and individualized treatment plan, stabilization and remission can be achieved in over 80% of patients. The prognosis is particularly good for children.