Chronic Inflammatory Demyelinating Polyneuropathy:  A Case Report

 

S Sreeni, Lakshmi R*

Department of  Pharmacy Practice, Amrita School of  Pharmacy, Kochi, Amrita Vishwa Vidyapeetham, Amrita University, India

 

ABSTRACT:

Chronic inflammatory demyelinating polyneuropathy (CIDP) is a treatable autoimmune neuropathic condition, which characterize progressive and relapsing stages. Major clinical presentations are gradatory increasing sensory loss and weakness interrelated with loss of reflexes. Relapse can occur at any time for CIDP patients. Diagnosis is based on cerebrospinal fluid protein, electromyography, nerve conduction velocity (NCV) test, peripheral nerve biopsy and electron micrograph of peripheral nerve. Standard treatments for CIDP are corticosteroids, Intravenous Immune Globulin (IVIG), plasma exchange or plasmapheresis. Second line drugs commonly used are immunosuppressant and immune modulatory agents, there are usually chemotherapy drugs which should be only given in special circumstances by specialist in their use. A 55 year old female encountered in the department of neurology, old case of Guillain-Barre Syndrome (GBS) was treated with steroids, later developed CIDP and was on reduced dose of prednisolone. Now presented with complaints of numbness and difficulty in walking, diagnosed to have CIDP relapse. Started treatment with corticosteroid [Tab. Wysolone (prednisolone) 50mg 1-0-0] and immunosuppressant [Tab. Cellcept (mycophenolate mofetil) 500mg 1-0-1]. Patient had significant improvement in symptoms. This case of CIDP relapse is effectively treated with corticosteroid and immunosuppressant with tapering of steroid dose.

 

 

INTRODUCTION:

Chronic inflammatory demyelinating polyneuropathy is an acquired polyneuritis, where there is inflammation of the nerve roots of peripheral nerves and myelin sheath over the nerves. CIDP can start at any age. Incidence of CIDP among adults is 1.0-1.9 per 1,00,000 and men are more prone than women¹. Nerves starts from the spinal cord to the rest of the body, insulating myelin sheath of the nerve allows electrical impulses to travel along the axon.

 

Demyelination describes a pathological process of destruction in the myelin supporting cells, that is oligodendrocytes and schwann cells or myelin lamellae with relative preservation of the axon (Fig.1). When demyelination takes place, electrical impulse is slowed or lost and messages transmitted from brain becomes discontinuous. There are multiple triggers which woke both cellular immunity (T-cell activation) and humoral immune system (immunoglobulin and complement deposition on myelinated nerve fibres)².

 

Fig.1: Image of neuron showing demyelination of myelin sheath³

 

Clinical variants of CIDP have similar symptoms. Comparison of these disorders will be useful for differential diagnosis, which include Lewis-Summer syndrome likely to be known as multifocal acquired demyelinating sensory and motor neuropathy (MADSAM), Charcot-Marie-Tooth disease, Distal acquired demyelinating sensory neuropathy (DADS), without IgM para-protein, Multiple sclerosis and few more⁴.

 

The symptoms are slowly progressive over 2 months, symptoms like symmetric weakness of both muscles around the hip, shoulder, arms and feet (both proximal and distal muscles). Alteration of nerve signal due to demyelination cause impaired motor function, abnormal or loss of sensation. Some alteration of sensation causing numbness, incoordination, tingling or prickling sensation. Other symptoms like burning, clumsiness, fatigue, pain, difficulty in swallowing and double vision. Walking will be abnormal and response to various sensory stimuli will be impaired. Neurologic examination will show atrophy. Deep tendon reflexes are reduced or absent⁵.

 

CIDP can be difficult to diagnose. Diagnosis is made primarily based on the clinical presentation of the patient and neurophysiological findings. Most experts consider symptoms of more than 8 weeks duration for the diagnosis of the disease. CIDP patients are commonly observed with the presence of proximal weakness in the context of a neuropathy, which suggests the impairment of nerve roots. Early evaluation can be done by nerve conduction velocity studies, which clearly shows demyelination with slow nerve conduction, prolonged distal latencies, temporal depression and prolonged F-wave latencies pointing the deformity of spinal roots. Loss of compound

 

Fig.2: Clinical Symptomatology as per the study done in 35 cases of Peripheral Neuropathy, AFMC study¹

 

Muscle action potential (CAMPs) and sensory nerve action potentials (SNAPs) can be identified by neuro physiological studies performed during later stage of the disease or in severe cases. NCV and Electromyography (EMG) test can be done to identify whether the disorder is purely peripheral neuropathy and is demyelinating. Cerebrospinal fluid analysis is done to identify increased protein levels, small amount of patients have mild lymphocytic pleocytosis and increased gamma globulin. MRI of the spine with gadolinium enhancement may be warranted. Peripheral nerve biopsy is considered if the diagnosis is not completely clear, when profound axonal involvement is observed on EMG or other causes cannot be excluded. Electron micrograph of peripheral nerve of patient with CIDP shows “onion bulb” formation in the myelin sheath due to continuous demyelination and remyelination^6,7. CBC, biochemistry profile, ANA level, ESR, serum and urine, immunoelectrophoresis are studied to exclude associated systemic infection. In some instances, genetic testing is also followed.

 

Gold standard for treatment of CIDP is Corticosteroids. ‘Corticosteroid’ or ‘corticoid’ includes natural gluco corticoids and mineralocorticoids and their synthetic analogues. Prednisone and prednisolone can be used as initial treatment in CIDP patients. Gluco corticoids maintain the normal level of excitability and the level of perception. These drugs suppress the inflammatory response by covering all components and stages of inflammation. Corticosteroids can be used in conjunction with other drugs such as immune suppressive drugs. Side effects include weight gain, cushingoid appearance, easy bruising and skin fragility, cataracts, aseptic necrosis of femoral or humeral heads, diabetes, osteoporosis etc and can deter long-term therapy^8,9. Plasma exchange (PE) is a procedure for removing toxins, metabolic substances and plasma parts, which comprise of pathogenic antibodies, circulating immune complexes, inflammatory mediators, pro-inflammatory cytokines and compliment from patient’s circulation. Blood is taken from the patient and blood cells are separated from plasma. The red blood cells are then re-infused with other human plasma, which consist of human albumin and saline. Patient frequently relapse after stopping PE. PE is an invasive therapy and can result in adverse effects related to venous access, haemorrhage and hemodynamic changes. Intravenous Immune Globulin (IVIG) is used to treat disorders of the immune system, IVIG are naturally occurring antibody obtained from healthy volunteers, which consist of pooled, polyvalent serum IgG from a large number of donors. Very high doses are usually used for initial treatment of CIDP patients and majority of the patients requires continued intermittent treatments. These regimens do have unacceptable side effects, so different immunotherapies   like immunosuppressants (Eg- Aza thioprine, Cyclosporine, Mycophenolate mofetil, Metho trexate, Etanercept etc) or immunomodulatory (Rituximab, Natalizumab, Alemtuzumab, Eculizumab, Fingolimod, cyclophosmphamide) can be used as an alternative or can be used in conjunction with the first line therapy¹⁰. Post treatment life depends on whether the disease was caught early enough to benefit from the treatment option. Gradual onset of CIDP delay the diagnosis and can result in significant nerve damage, leading  to slow response to the therapy. Chronic CIDP need long term care¹¹.

 

CASE REPORT:

A 55 year old female was admitted in neurology with a known case of diabetes mellitus since 1 month (at the time of admission GRBS: 345 mg/dl) and was on no medication, hypothyroidism since 4 years and was on Tab. Thyronorm 25mcg 1-0-0. She was diagnosed to have Guillain-Barre Syndrome (GBS) 23 years back and was resolved with steroids, Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) and Psoriasis vulgaris (steroid induced) was diagnosed 1 year back and she was on low dose Tab. Wysolone (prednisolone) 5 mg 1-0-0. Patient was apparently alright for the last 8 months.

 

Now presented with complaints of numbness of both lower limbs from knee up to feet and difficulty in walking since 2 months.  Patient was having difficulty in walking with imbalance and buckling of both knee. Foot drop was also present. History of difficulty in gripping footwear was present and numbness of both upper limbs, starting from hands up to elbow joint which was associated with slippage and difficulty in gripping objects. Occasional numbness over the head and arms which increased on keeping arms in abduct position. There is also history of numbness in bother upper limb from elbow up to hands. With these complaints she was admitted in a nearby hospital where she was started on Tab. Wysolone (Prednisolone) 40mg 1-0-0 and there was no improvement in the condition, so she came to our hospital for further management.

 

On admission patient was conscious and oriented, Tab. Wysolone (prednisolone) 40mg, 1-0-0 dose was increased to 50 mg. Cranial nerves were normal. Tone was decreased. Power was 4/5- for hip flexion, 3/5 for left EHL and 4+/5 for other muscles in lower limb. Sensory system was normal except for impaired vibration sense in lower limbs. Reflexes were sluggish with plantars flexor. Based on history and physical examination possibility of CIDP relapse was considered. Nerve Conduction Velocity (NCV) test was done which showed predominantly demyelinating type of sensory & motor radiculoneuropathy affecting both upper and lower limbs. Patient was started on Inj. Methyl prednisolone 1gm IV OD for 5 days and also on Tab. Cellcept (mycophenolate mofetil) 500mg BD with strict monitoring of glucose levels and infection parameters. Endocrine consultation was done and their advise (adding Inj. H. actrapid 25-16-14 units S/C ½ hour before food, Inj. Lantus (insulin glargine)15 units S/C @ 10pm, Tab, Metformin  500mg 1-0-1 )followed for glycemic control. Patient had gradual improvement in symptoms with this treatment and discharged with plan to taper steroids during follow up based on the effects of immunosuppressant (mycophenolate mofetil).

 

DISCUSSION:

Chronic inflammatory demyelinating polyneuropathy (CIDP) is an autoimmune heterogeneous disorder affecting the peripheral nerves, causing sensory symptoms and motor symptoms and signs. CIDP starts insidiously and evolves either slowly progressing or relapsing manner. Our patient, who had been in remission for 1 year developed symptoms and numbness of both lower limbs from knee up to feet and difficulty in walking since 2 months, diagnosed to have CIDP relapse. In a study conducted by Gorthi CS took 35 cases of peripheral neuropathy the major symptoms seen are weakness and numbness (71%), the  same symptom of numbness and muscle weakness had appeared in our patient¹ (Fig.2). NCV test is used for diagnosis showing motor and sensory radiculoneuropathy¹². Mauley SA, Kelkar P, Parry studied 3 women and 7 men with CIDP for 22 months, treated with steroid regimen. Treatment lead to remarkable improvement in weakness and disability, only 1 patient discontinued due to adverse effects ¹³. Our patient taking steroid encountered with relapse. Added Mycophenolate mofetil and decided to reduce the dose by titrating steroids. Bedi G, Brown A, Tong T, Sharma KR evaluated the effect of myco phenolate mofetil in a database of 184 patients with CIDP, six of the eight patients who met the inclusion criteria were able to stop the concomitant medication¹⁴. Chaudhry V, Cornblath D R., Griffin J W., O'Brien R, Drachman D B in 2001 treated 38 patients with myco phenolate mofetil, all patients recieved the drug without any major adverse effects¹⁵. Here in our case the same strategy is adopted, since the patients had shown significant improvement in symptoms after adding Mycophenolate mofetil. Planned to taper steroid by analysing the efficacy of the immunosuppressant.

 

CONCLUSION:

CIDP is a relapsing polyneuropathy. So regular follow up is needed to identify the early symptoms in CIDP relapse patients. Patient treated with Tab. Wysolone (prednisolone) and Tab. Cellcept (mycophenolate mofetil) attained good improvement in symptoms in a short span of time when compared with the steroid therapy initiated 1 year ago, after CIDP was diagnosed. Treating CIDP with immunosuppressants for the patients on steroid therapy for a long time is found to be effective in relapse conditions and the steroid dose can be titrated according to the efficacy of immunosuppressant. Gradually steroids can be stopped.

 

CONFLICT OF INTERESTS:

Declared None

 

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Accepted on 28.08.2016        © RJPT All right reserved

Research J. Pharm. and Tech 2016; 9(12):2165-2168.

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