Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP)_2
Short Summary

43-year-old male presented with paresthesias in bilateral distal limbs. EMG showed demyelinating neuropathy with motor conduction blocks in ulnar and median nerves. The diagnosis was CIDP with less likely possibility of MMN. His total cholesterol and triglycerides values were elevated and Liponorm was started for cholesterol, which worsened the paresthesias so that was stopped. Patient was treated with steroids without improvement, until he received IV deltacortene, which improved symptoms for 1 month before worsening again and now involve the lower limbs. His current treatment is steroids.

Patient's Questions
1)        Do you confirm the diagnosis?
 
2)        What therapy do you suggest? In case the therapy performed is the best one could you advise eventual experimental therapies?
 
3)        Centers of excellence in Italy and/or in Europe?
 
4)        Prognosis?
Medical Background

Age: 43, Sex : Male
Diagnosis: Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP)  
Anamnesis:  Family hypercholesterolemia.
                        No other relevant disease.
Case history:
Symptomatic beginning in April 2006 with the appearance of parestesies at distal upper limbs, much more on the right side and more in the median nerve territory. As the clinical picture persisted, electromyography (EMG) was performed with evidence of a demyelinating neuropathy at the upper limbs with the ulnar and median nerve motor conduction block at the elbow, bilaterally.
The patient was, therefore, hospitalized at the Legnano Hospital from for medical tests.
The neurologic exam at admission highlighted: distal hypoesthesia of upper limbs, much more evident for the tactile modality, less evident for the thermodolorific and vibratory one, asymmetric as more marked in the right side and in the median nerve territory.
An EMG was repeated, it confirmed that the demyelinating neuropathy picture, with motor conduction blocks of the upper limbs, remained unchanged.
Among the biohumoral tests performed, serum protein electrophoresis, Reumafactor test, ERS, oncogenic markers, C-reactive protein, anti-Borellia antibodies were within norm limits. On the contrary, these values were altered: cholesterol: 269 mg/dl, triglycerides: 292 md/dl.
Instrumental examinations performed:
ECG: synusal rhythm 64/min.
Chest X-ray: no parenchymal lesions.
Diagnostic rachicentesis with injection needle 22 after local anesthesia with lidocaine 3 cc: the chemical and physical outline was within norm limits (proteins 42.7 mg/dl, 1 cell).
Therefore, the diagnostic conclusion of hospitalization were indicative of:
“the instrumental clinical picture is compatible with a diagnosis of Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP)
in the upper limb demyelinating variant (Upper limb demyelinating CIDP). The presence of symptoms and sensitive objective signs leaves out a multifocal motor neuropathy (MMN)”.
The patient was followed by the specialist in neurology and a therapy with Prednisone 100 mg daily was therefore diagnosed at the patient’s discharge, highlighting the importance of a close longitudinal follow up for possible further medical tests and therapies.
The steroid dosage was gradually reduced in time: 50 mg daily from January 2007; 25 mg daily from May 2007; in July 2007 the dose of 25 mg every other day was reached.
In addition, from mid-June 2007 liponorm for hypocholesterolemizing therapy was introduced. It seemed to accentuate the hand paresthesias, forcing the endocrinologist to recommend the suspension of that medication from July 2007.
After a brief improvement during the therapy with the steroid, the symptoms came back with involvement of both hands, especially of the1st -2nd-4th finger and reduction of the hands motility.
Therefore, in July 2007, the patient decided to contact neurologist at the Negrar Hospital (VR), who asked him to undergo further medical tests:
-           cervical spine and encephalon MRI turned out negative, with the exception of a small discopathy C6/C7.
-           EMG upper limbs with evidence of partial block of the ulnar nerve motor conduction, bilaterally and small block on the median nerve on the right, SAP within norm limits.
The results were substantially comparable to the previous ones, so the patient continued the treatment with deltacortene 5 mg daily without any relevant symptomatic improvement.
In December 2007 EMG was repeated, the results were always the same and the patient continued the treatment with Deltacortene untill May 2008 when at the Borgo Roma Hospital (VR) an intravenous cortisone drip was performed for 1 week. After an improvement lasted 1 month, the symptoms reappeared involving ad worsening the lower limbs too.

Expert's Opinion

Recommendations:
I have reviewed the notes provided and agree that the patient has features of CIDP. However, the diagnosis of CIDP is difficult and there is spectrum of CIDP that is heterogenous and there are many sets of diagnostic criteria that have been established. Given the patient's age, history, and study data, I would recommend the following given the diagnosis of CIDP.
1) Do you confirm the diagnosis?
This is a difficult issue and distinguishing between CIDP and variants that are similar can be difficult and a trained neuromuscular specialist is needed to make an accurate diagnosis. There are inherited polyneuropathies that can sometimes be confused with acquired polyneuropathies (chronic, acquired, immune mediated, and demyelinating). Similarly, sometimes the neuropathy can be demyelinating or purely axonal or mixed and that can also be difficult to diagnose. But sub-categorization is important to treat effectively. One must also be aware of other diagnoses that can mimic CIDP such as diabetic polyneuropathy, amyotrophic lateral sclerosis, paraprotein, anti-MAG antibody, guillian-barre syndrome, etc.
To further evaluate, would recommend:
A) Repeat LP to see if inflammation is present since patient is progressing.
B) Nerve biopsy would be helpful in lower extremities since they are now involved and the pathology might give clues to a definite diagnosis
C) Review family history-it is important and despite not having a formal diagnosis yet, it would be good to have family members seen by a doctor to see if any features of demyelinating polyneuropathy to make sure that this is not an inherited condition
D) Would have the neurologist review a recent recommendation regarding work-up to be sure of accurate and full work-up as detailed below
French CIDP Study Group. Recommendations on diagnostic strategies for chronic inflammatory demyelinating polyradiculoneuropathy. J Neurol Neurosurg Psychiatry. 2008 Feb;79(2):115-8. Review.
 
2) What therapy do you suggest? In case the therapy performed is the best one could you advise eventual experimental therapies?
-       Intravenous immunoglobulin (IVIG) can be helpful (please check that patient is not IgA deficient)

-       If steriod dependant can transition to cytotoxic immunosuppresive therapy cyclosporine 3 mg/kg/day, with plasma trough concentrations between 100 and 150 ng/ml. If patients respond to cyclosporin, remission can be maintained for 2 years, after which the dose can be slowly reduced over 1 year. Eventual withdrawal should be considered.

-       Plasmapheresis

-       Rituximab a monoclonal anti-CD20 antibody against B-cells maybe an effective option for such patients if above fails and would represent the most investigational option but also maybe the most potent.

-       Physiotherapy may improve muscle strength, function and mobility, and minimize the shrinkage of muscles and tendons and distortions of the joints.
3) Centers of excellence in Italy and/or in Europe?
Milan: Giovanni Meola, Eduardo Nobile-Orazio
Netherlands: Drs. Van den Berg, Vermeulen, and van der Meche
4) Prognosis?
The course of CIDP varies widely among individuals. Difficult to predict how any 1 patient will respond to a specific treatment. But in general we should be able to rule out an inherited demyelinating polyneuropathy and if so then for the inflammatory demyelinating polyneuropathy treatment plan is as above. And most people do respond well to 1 of the treatments for long periods of time of remission.
All of these recommendations have to be taken in context of functional status and balancing quality of life.

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