The neurological manifestations of malabsorption W . T . COOKE

MALABSORPTION syndromes are clinical disorders arising from disturbances of small intestinal function although pernicious anaemia is not usually included in this category. The principal disorders are coeliac disease, post-gastrectomy states and small intestinal diverticulosis. Tropical sprue and regional enteritis both with a high incidence of low levels of serum vitamin B12 are also included and, for completeness, Whipple's disease which occasionally presents with a neuropathy must also be included (Maizel Ruffin and Dobbins, 1970). In some of these disorders, the neurological manifestations of vitamin B12 deficiency will occur, sometimes with peripheral nerve, spinal cord or cerebral symptoms being the first evidence. They are well recognized as occurring in post-gastrectomy states where the incidence of vitamin B12 deficiency 10-15 years after operation is high (Williams et al., 1969) and small intestinal diverticulosis (Cooke et al., 1963). They do not, however, appear to occur in tropical sprue, regional enteritis or in coeliac disease despite the high incidence of low serum levels of vitamin B12. However, when such neurological disorders have been excluded, there remain many patients with post-gastrectomy states, small intestinal diverticulosis or with coeliac disease (Cooke and Smith, 1966) in whom cerebral manifestations, spinal cord lesions or peripheral neuropathy appear unrelated to any obvious aetiological factor such as vitamin B12 deficiency, platybasia and osteomalacia (Hurwitz and Banerji, 1972), Wernicke's syndrome, chronic electrolyte depletion or the myopathy of vitamin D deficiency (Smith and Stern, 1967). Much of the work concerning these neurological complications has been done with coeliac disease, but there is little clinical difference to be detected in the clinical situations in other disorders of the small intestine. In passing, it should be noted that this type of neurological disorder displays surprisingly close similarity to carcinomatous neuropathy. To consider first the manifestations of organic nerve involvement (and secondly the mental and psychological associations), the neuropathy affects the limbs principally and the legs in particular with numbness, tinglings, pain, weakness and unsteadiness of gait. Indeed, ataxia rapidly becomes the major symptom. Although the arms are less commonly affected, some patients are unable to write steadily or undo buttons. Ankle jerks are lost early: evidence of posterior column involvement is marked in the legs whilst sensory impairment of glove and stocking type is frequent. Ataxia is usually of the postural type but cerebellar signs are present in some. Attacks of unconsciousness occur in many patients. The pathological findings are striking (Cooke and Smith, 1966; Cooke, Johnson and Wolff, 1966). In two thirds of the #uthor's patients, there was atrophy and focal loss of neurones, sufficiently marked in some cases tor the cortical atrophy to be noted macroscopically, the nerve cells being replaced by a retiform network of glial fibres and in some there was also astrocyte hypertrophy accompanied by neuronal degeneration. Spinal cord lesions tend to be patchy and non-systematized with spongy demyelination of the posterior and lateral columns with variable degrees of axonal degeneration and little gliosis. In the peripheral nerves, there was collateral branching and re-innervation with diffuse swellings of the terminal axons. On electron microscopy, these terminal axons showed gross disorganization of the internal structure with breaking up of presynaptic membrane, multivesicular and electron-dense bodies, degenerated mitochondria and a curious 'frog-spawn' cytoplasm (Cooke et al.,