Advances in Neurology and Neuromuscular Diseases

Our patient, a 20 year old girl, presented to us with complaints of aches and pains of all four limbs of 18 months. 6 months later she started developing thigh cramps and progressive weakness predominantly of lower limbs.  A detailed history revealed anorexia, weight loss of 15 months and a history of delayed menarche. On examination, she was malnourished and had pallor. Her general examination showed angular cheilitis and bitots spot.  Neurological examination showed pure motor, symmetrical proximal muscle weakness of both lower limbs. There was no wasting or fasciculations. All deep tendon reflexes were normal. Initial differential diagnosis included chronic infection associated myopathy, nutritional myopathy – secondary to malabsorption syndrome and inflammatory myopathy. On investigating, the blood showed low Hemoglobin (7.5gm/dl) with low MCV, ferritin  and peripheral smear suggestive of iron deficiency anemia, mild elevation CPK (540). Other metabolic workup showed low ionized calcium and phosphorus with a high alkaline phosphatase level of 516. Viral markers screening, chest Xray, USG abdomen and endocrinology workup for thyroid, parathyroid, pituitory were negative. Vitamin D level was very low (less than 3ng/ml). A possibility of osteomalacic myopathy due to vitamin D deficiency was considered and correction was given. With high dose vitamin D3 replacement (60000 units daily for 10 days) she started showing response and her cramps and pain got reduced and she was able to walk independently without any support by 2nd week of starting treatment. A diagnosis of osteomalacic myopathy was made and weekly vitamin D was given. Malabsorption work up including stool routine was negative. A colonoscopy done was apparently normal. However a biopsy was taken from apparently normal mucosa which showed non-caseating granulomatous inflammation consistent with Crohn’s disease. She was planned for a muscle biopsy to look for ANCA positive immune vasculitis causing subacute myopathy, but was refused by bystanders. She was started on definitive treatment for crohns disease and was asymptomatic at 6 months follow up with no residual neurological deficits.

Discussion

        History and physical examination are critical components to appropriate diagnosis. Temporal evolutions of symptoms and age of onset help to narrow down your differential diagnosis. Differential diagnosis for acquired myopathy includes endocrine, metabolic, inflammatory, paraneoplastic, drug induced, critical illness myopathies and myopathy acquired with infectious causes. Our patient had crohns disease with osteomalacic myopathy. Evaluation of patients with metabolic causes of muscle weakness remains a challenge due to frequent lack of clinical symptoms. Typical manifestations include exercise induced myalgias, exercise intolerance, and cramps. Myopathies are caused by either excess or deficiencies of some of these minerals including potassium, calcium, phosphorous, magnesium, and vitamin D.

       Muscle involvement is a rare extraintestinal manifestation in IBD. Myopathy can be related either to therapy of IBD (steroids, 5‐ASA, and azathioprine) or to disease‐related myositis or to a coexistent autoimmune disorder affecting the muscle. Antigenic release due to bowel inflammation with subsequent antibody production and immune complex formation has been postulated as a possible pathogenetic mechanism of muscular involvement in IBD. Clinical studies have confirmed that vitamin D deficiency is common in this patient group. Musculoskeletal manifestations include arthritis, osteoporotic fractures, orbital myositis, polymyositis, gastrocnemius myalgia syndrome and fibromyalgia, but with preceding gastrointestinal symptoms. However crohns disease presenting as myopathy is rare.

       Vitamin D deficiency can occur from decreased intake, decreased absorption, or impaired vitamin D metabolism (as in renal disease). Neurological manifestations include ataxic neuropathy due to loss of proprioception and myopathy with proximal weakness. Pain reflects the underlying bone disease (osteomalacia).  Screening for vitamin D deficiency is essential as one of the treatable causes of acquired myopathies. Vitamin D has an immunomodulator action. An increasing number of epidemiological, genetic, basic science and animal model studies support the concept that vitamin D regulation may partly determine occurrence and course of IBD, which warrants further study. Data is starting to emerge that identifying those with a deficiency and correcting may improve health outcome measures in terms of symptomatic improvement and crohns disease activity index.

Conclusion
Myopathy as the presenting symptom in crohns disease is a rare presentation. Vitamin D deficiency is common among patients with crohns disease. Vitamin D supplementation to this group of patients improve the symptoms and quality of life by its potential role as a immunomodulator and disease modifier. A detailed history and the step wise approach to a patient with muscle weakness can be extremely helpful in narrowing the differential diagnosis in myopathy of systemic diseases. Recognition is extremely important as most of these are reversible when diagnosed and managed in a timely fashion and thus carry a good prognosis.