Subacute combined degeneration of the spinal cord

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72 Subacute combined degeneration of the spinal cord

Instruction

Carry out a neurological examination of the patient’s legs.

Salient features

History

• Family history of pernicious anaemia

• History of alcohol consumption and previous gastrectomy

• History of chronic diarrhoea (Crohns’ disease, etc.)

• Tingling distal paraesthesia (common presenting symptom)

• Whether the patient is a vegan.

Examination

• Absent ankle jerks (caused by 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:

• mucous membranes for anaemia (pernicious anaemia)
• abdomen for scars of previous gastrectomy (carcinoma of the stomach)
• pupils (Argyll Robertson pupil (Case 39) because tabes is a differential diagnosis)
• fundus for optic atrophy, seen in this condition.

• Tell the examiner that you would like to do the following investigations:

• Mini-mental status examination for dementia
• A ‘red tongue and unsteady gait’ is seen in the classic condition.

Diagnosis

This patient has absent ankle jerks, brisk knee jerks and upgoing plantars with posterior column signs (lesion) caused by subacute combined degeneration of the spinal cord (aetiology) and paralysis (functional status).

Questions

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).

Advanced-level questions

What is the pathology of this condition?

There is degeneration of the axons in both the ascending tracts of the posterior columns (sensory) and the descending pyramidal tracts (motor), hence combined degeneration.

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 (no longer done because radioisotope is not available in UK)

• MRI findings are diverse (Fig. 72.1) but vitamin B12 deficiency should be considered in differential diagnosis of all spinal cord, peripheral nerve and neuropsychiatric disorders (J Neurol Neurosurg Psych 1998;65:822–7).

image

Fig. 72.1 Subacute combined degeneration of the spinal cord in vitamin B12 deficiency. (A) T2-weighted MRI shows abnormal signal intensity of spinal cord extending from C1 toC6 (arrows). (B) There is no enhancement after application of gadolinium in the sagital T1-weighted image.

(With permission from Schöllhammer M et al. 2005.)

If this patient had a haemoglobin level of 6 g/l, how would you treat it?

Avoid giving packed cells before replacing vitamin B12 as this may irreversibly exacerbate the neurological manifestations. Furthermore, blood transfusion is reported to precipitate incipient heart failure and death.

What type of anaemia may be seen in such patients?

Macrocytic anaemia.

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: blocking antibody that prevents vitamin B12 from binding to intrinsic factor; occurs in 55% of patients

Type 2: binding or precipitating antibody, which reacts with intrinsic factor or with vitamin B12–intrinsic factor complex and is seen in 35% of patients.

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 do in an asymptomatic patient with pernicious anaemia?

In the absence of GI symptoms, gastroscopy or barium meal is not indicated, although many physicians tend to perform one of these investigations.

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 B12?

The response to vitamin B12 therapy is variable: it may improve, remain unchanged or even deteriorate. Sensory abnormalities improve more than motor abnormalities and peripheral neuropathy responds to treatment better 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 P Murphy (1892–1987) of Harvard Medical School and Peter Brent Brigham Hospital, Boston, for their discoveries concerning liver therapy in anaemia. This condition is also known as Addison–Biermer’s anaemia with reference to Thomas Addison and the German physician Anton Biermer.

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.

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