1 g/dl) and volume (10dos fl ?m 3 ). The vitamin Btwelve level was borderline low (203 pg/ml), with a borderline pathological Schilling test (9.85% absorption; after substitution of intrinsic factor, % absorption). Antibodies specific for thyroglobulin, parietal cells, and microsomes were not detectable. Stool tests for parasites were negative. A gastroscopy was refused by the patient. The CSF had a normal cell count but an elevated protein content (59 mg/100ml), indicating a disturbed blood–CSF barrier.
Psychological testing was difficult to perform and revealed an average overall IQ (104). Short-term memory was severely impaired and cognitive flexibility was reduced. The patient was treated with vitamin B12 in combination with an antidepressant (clomipramine) and initial anxiolytic medication (lorazepam). A second psychological testing was refused by the patient. On dismissal from the clinic, in contrast to the time of admission, he was fully oriented and his mood was balanced.
Scientific Features
Apart from the well-characterized hematological changes of vitamin B12 deficiency, a variety of neurological impairments have been described. Typically, signs of peripheral neuropathy and myelopathy can be observed: distal paresthesias, impairment of vibratory and position sense, reduced ankle jerks, Lhermitte’s sign. 1 In more severe cases symmetrical limb weakness and other pyramidal deficits can occur 2–4 (Table 1). Paresthesia is the most common initial complaint, affecting more than 70% of the patients with neurological symptoms. 4 Electrophysiological signs of demyelination can be detected in tests of nerve conduction velocity and somatosensory evoked potentials. 5
Related Mental Change
Possible links between vitamin B12 deficiency and cerebral symptoms were first observed in patients who suffered from funicular myelosis or pernicious anemia. 6,7 Today there is an increasing evidence that hematological and neuropsychiatric effects due to cobalamin deficiency do not necessarily occur simultaneously. 3,8–11 The true incidence of cerebral symptoms in vitamin B12 deficiency is unknown; reports vary between 4% and more than 50%, 2,10,12,13 depending on the population studied and the definition of vitamin B12 deficiency used. The mental effects described in the context of cobalamin deficiency cover a scope from mood changes (agitation, depression, mania) to psychotic episodes (paranoia, auditory and visual hallucinations, delusions) to cognitive impairment (slow mentation, memory deficits, confusion, dementia) 2,4,10,11,13 (Table 1). Mental or psychological changes may precede hematological signs by months or years-they can in fact be the initial or only symptoms. 3,9,14 In a study with patients suffering from vitamin B12 deficiency after gastric resections, 50% displayed intellectual impairment, whereas only 14% had megaloblastic bone marrow. 12 However, most or all patients with central nervous system involvement also show some signs of peripheral neuropathy. 15
Cobalamin deficiency lonely dating apps has been shown to be the most frequent associated physical disease in patients with dementia. 16 The incidence of low vitamin B12 levels among dementia patients has been found to range between 29% 8 and 47%. 17 Even in healthy elderly patients, a correlation between serum cobalamin level and cognitive function (as tested in IQ, MMSE, verbal, and memory tests) has been observed. 18,19 Other studies, on the contrary, have questioned the correlation between dementia and serum cobalamin levels and the reversibility of dementia under cobalamin substitution (see review 20 ). Furthermore, low serum cobalamin levels have also been detected in healthy control subjects 21 and nondemented patients with other neurological diseases (our own observation).
Pathophysiology
Historical reports describe perivascular degeneration and foci of myelin degeneration in the brains of patients with pernicious anemia. 6,22 MRI images of patients with vitamin B12 deficiency sometimes show signs of disseminated demyelination similar to those found in multiple sclerosis. 23 A number of animal models provide additional evidence for the detrimental effect of vitamin B12 deficiency on the integrity of myelin, 24,25 which is aggravated under the oxidizing influence of N2O. 26,27 The exact mechanism of the myelin damage following cobalamin deficiency, however, is still unknown. 28,29