Carry out a neurological examination of the patient's legs.
· Family history of pernicious anaemia.
· History of alcohol consumption and previous gastrectomy.
· History of chronic diarrhoea (Crohn's disease, etc.).
· Tingling distal paraesthesia (common presenting symptom).
· Whether the patient is a vegan.
· Absent ankle jerks (due to peripheral neuropathy and motor involvement).
· Brisk knee jerks.
· Upgoing plantars (usually first evidence of spinal cord lesion).
· Diminished light touch, vibration and posterior column signs.
· Romberg's sign positive.
Proceed as follows:
· Examine the following:
-Mucous membranes for anaemia (pernicious anaemia).
-Abdomen for scars of previous gastrectomy (carcinoma of the stomach).
-Pupils (Argyll Robertson pupil because tabes is a differential diagnosis).
-Fundus for optic atrophy, seen in this condition. · Tell the examiner that you would like to perform the following investigations: -A
mini-mental status examination for dementia.
This patient has absent ankle jerks, brisk knee jerks and upgoing plantars with posterior column signs (lesion) due to subacute
combined degeneration of the spinal cord (aetiology) and paralysis (functional status).
Mention a few causes of vitamin B12 deficiency.
· Vegan diet.
· Impaired absorption:
From the stomach (pernicious anaemia, gastrectomy).
-From the small bowel (ileal disease, bacterial overgrowth, coeliac disease). -From the pancreas (chronic pancreatic disease). -As a
result of fish tapeworm (rare).
What is the pathology of this condition?
There is degeneration of the axons in both the ascending tracts of the posterior columns and the descending pyramidal tracts (hence
How would you investigate such a patient?
· FBC and reticulocyte count.
· Vitamin B12 and folate concentrations.
· Serum ferritin levels (since associated iron deficiency is common).
· Bone marrow examination.
· Parietal cell and intrinsic factor antibodies.
· Schilling test.
· MRI findings are diverse but vitamin B12 deficiency should be considered in differential diagnosis of all spinal cord, peripheral
nerve and neuropsychiatric disorders (J Neurol Neurosurg Psychiatry 1998; 65: 822-7).
If this patient had a haemoglobin level of 6 g/dl, how would you treat it?
I would avoid giving packed cells before replacing vitamin B12 as this may irreversibly exacerbate the neurological manifestations.
Furthermore, blood trans-fusion is reported to precipitate incipient heart failure and death.
What type of anaemia may be seen in such patients?
Mention a few other causes of macrocytic anaemia.
· With megaloblastic bone marrow: vitamin B12 deficiency, folate deficiency.
· With normoblastic marrow: haemolytic anaemias, post-haemorrhagic anaemia, severe hypoxia, myxoedema, hypopituitarism, bone marrow
infiltration, acute leukaemia and aplastic anaemia.
What do you know about intrinsic factor antibodies?
Intrinsic factor antibodies are seen in about 50% of patients with pernicious anaemia. About 45% of the patients have no antibody to intrinsic factor.
There are two types of antibody:
· Type 1 - the blocking antibody which prevents vitamin Bi2 from binding to intrinsic factor and occurs in 55% of patients.
· Type 2 - the binding or precipitating antibody, which reacts with intrinsic factor or with vitamin B12-intrinsic factor complex and is seen in 35%
What is the relationship between pernicious anaemia and gastric carcinoma ?
The incidence of gastric carcinoma in patients with pernicious anaemia is increased three-fold compared with that in the general population.
What gastrointestinal investigations would you perform in an asymptomatic patient with pernicious
In the absence of gastrointestinal symptoms, gastroscopy or barium meal is not indicated, although many physicians tend to perform one of these
What do you understand by the term 'combined' degeneration of the cord?
This refers to the combined demyelination of both pyramids (or lateral columns) and posterior columns of the spinal cord.
What is the response of the neurological lesions to treatment with vitamin B127
The response to vitamin B12 therapy is variable: the lesions may improve, remain unchanged or even deteriorate. Sensory abnormalities improve
more than motor abnormalities, and peripheral neuropathy responds better to treatment than myelopathy.
Subacute combined degeneration is also known as Putnam-Dana syndrome or Lichtheim's disease. James Jackson Putnam (1846-1918) and Charles
Loomis Dana (1852-1935) were both US neurologists.
Ludwig Lichtheim (1845-1928), a German physician.
Pernicious anaemia was usually fatal until 1926, when Whipple, Minot and Murphy described the beneficial effects of feeding liver. The 1934 Nobel
Prize in Medicine was awarded jointly to George Whipple (1878-1976) of University of Rochester, New York, and to George Minot (1885-1950) and
William I~ Murphy (1892-1987) of Harvard Medical School and Peter Brent Brigham Hospital, Boston, for their discoveries concerning liver therapy in
cases of anaemia.
William B. Castle first found that oral administration of gastric juice (intrinsic factor) or beef (extrinsic factor, i.e. vitamin B12) alone was not effective in
the treatment of pernicious anaemia but that a mixture of both these factors rendered the patient erythropoietically active. Castle worked with Francis
Peabody at the Harvard Medical School Unit at Boston City Hospital before he became Professor of Medicine at Harvard.