Pernicious anemia (PA) is a macrocytic anemia that is caused by vitamin B(12) deficiency, as a result of intrinsic factor deficiency. PA is associated with atrophic body gastritis (ABG), whose diagnosis is based on histological confirmation of gastric body atrophy. Serological markers that suggest oxyntic mucosa damage are increased fasting gastrin and decreased pepsinogen I. Without performing Schilling's test, intrinsic factor deficiency may not be proven, and intrinsic factor and parietal cell antibodies are useful surrogate markers of PA, with 73% sensitivity and 100% specificity. PA is mainly considered a disease of the elderly, but younger patients represent about 15% of patients. PA patients may seek medical advice due to symptoms related to anemia, such as weakness and asthenia. Less commonly, the disease is suspected to be caused by dyspepsia. PA is frequently associated with autoimmune thyroid disease (40%) and other autoimmune disorders, such as diabetes mellitus (10%), as part of the autoimmune polyendocrine syndrome. PA is the end-stage of ABG. Long-standing Helicobacter pylori infection probably plays a role in many patients with PA, in whom the active infectious process has been gradually replaced by an autoimmune disease that terminates in a burned-out infection and the irreversible destruction of the gastric body mucosa. Human leucocyte antigen-DR genotypes suggest a role for genetic susceptibility in PA. PA patients should be managed by cobalamin replacement treatment and monitoring for onset of iron deficiency. Moreover, they should be advised about possible gastrointestinal long-term consequences, such as gastric cancer and carcinoids.
Vitamin B12 deficiency is a systemic disease that often affects the nervous system. One of the most prevalent manifestations is subacute combined degeneration (SCD) of the spinal cord. To access the clinical, electrophysiological, and structural abnormalities associated with SCD, a study was conducted in nine patients.
Clinical, electrophysiological (electroneurography, somatosensory and motor evoked potentials), and MRI evaluations were performed in patients before and after treatment.
The most prominent clinical and electrophysiological findings in all patients were dysfunctions of the posterior column. Corresponding hyperintense lesions in the posterior column of the spinal cord were found in two patients by T2 weighted MRI. Damage to the central motor pathway was identified in four patients. Demyelinating neuropathy was present in one patient and axonal neuropathy in four. All patients showed improvement of their symptoms after treatment with cobalamin. Abnormalities of the spinal cord on MRI disappeared early in recovery. Motor evoked potentials and median somatosensory evoked potentials typically normalised after treatment, whereas tibial somatosensory evoked potentials remained abnormal in most patients.
Clinical, electrophysiological, and MRI findings associated with SCD in vitamin B12 deficiency are diverse. Thus vitamin B12 deficiency should be considered in the differential diagnosis of all spinal cord, peripheral nerve, and neuropsychiatric disorders.
Ataxia is unspecified motor clumsiness. This chapter overviews types of ataxia and focuses on cerebellar ataxia as a major type of ataxia. Pathophysiologically, cerebellar ataxia represents failure to maintain normal anti-inertia mechanisms that ensure smoothness, evenness, and accuracy of movements. The cerebellum and cerebellar pathways are affected in a variety of acute and chronic conditions that can cause ataxia. One should always remember that chronic or subacute cerebellar ataxia may result from tumors, normal pressure hydrocephalus, and paraneoplastic cerebellar degeneration. Chronic progressive ataxia is a key feature of idiopathic degenerative ataxic syndromes, both hereditary and sporadic. The diagnosis of patients with ataxic disorders is based, first of all, on neuroimaging and neurophysiological examinations, which provide important information about structural and functional characteristics of the central and the peripheral nervous system. Management and prognosis of ataxic syndromes rely on the primary cause of ataxia.
Autoimmune gastritis is the silent pathological lesion that may eventually become clinically manifest as pernicious anaemia after a latency of 20–30 or more years. Autoimmune or type A gastritis is restricted to the parietal cell-containing corpus of the stomach. Circulating autoantibody to gastric parietal cell H/K ATPase, the enzyme responsible for acidification of gastric juice, is a diagnostic marker for autoimmune gastritis. As parietal cell, autoantibody may also be found in relatives of patients with pernicious anaemia and with other autoimmune endocrinopathies such as autoimmune thyroiditis and type 1 diabetes mellitus, it is not diagnostic for pernicious anaemia. The advent of pernicious anaemia is accompanied by the development of autoantibody to intrinsic factor, itself a secretory product of gastric parietal cells. Intrinsic factor autoantibody, present in serum and gastric juice, can block intrinsic factor from binding to bind vitamin B12 and hinder absorption of the vitamin by cubulin receptors in the ileum. With the vanishing Schilling's test, increasing reliance is placed on autoantibody to intrinsic factor for the diagnosis of pernicious anaemia. However the sensitivity and specificity of commercial enzyme-linked immunosorbent assay (ELISAs) for diagnosis of the anaemia remains unknown. Both autoantibodies can antedate development of pernicious anaemia, but their predictive value is diminished because not all patients with either one or both of these antibodies will necessarily go on to develop anaemia.
There are a large number of causes of megaloblastic anaemia. The most frequent are disorders resulting in vitamin B(12) or folate deficiency. The diagnostic process often consists first of establishing the presence of B(12) or folate deficiency and then of determining the cause of deficiency. The blood count, blood film, serum B(12) assay, and red cell and serum folate assays are the primary investigations. Other useful investigations include serum/plasma methylmalonic acid (MMA), plasma total homocysteine (tHCYS) and serum holo-transcobalamin II assays. All currently used tests have limitations regarding specificity or sensitivity or both and the metabolite assays are not widely available. An understanding of these limitations is essential in formulating any diagnostic strategy. The wide use of serum B(12) and metabolite assays has resulted in the increasingly early diagnosis of B(12) deficiency, often in patients without B(12)-related symptoms (subclinical deficiency). Food cobalamin malabsorption is the most frequent cause of a low serum B(12). At least 25% of low serum B(12) levels are not associated with elevated metabolite levels and may not indicate B(12) deficiency. Some of these are caused by partial deficiency of transcobalamine I.