This Is MS Multiple Sclerosis Community: Knowledge & Support

The new neuro at Mayo, in reviewing the 12 vials of blood taken for the myriad of tests she ran, combined with the MRI of brain, spine (thoracic and cervical)

CLINICAL FEATURES

Polyneuropathy
Sensory change: 2° spinal or peripheral nerve lesions
.....Early: Paresthesias
.....Loss especially of large fiber modalities
.....Distal
Motor: Later in course; Distal
Reflexes
.....Tendon: Reduced or absent at ankles
.....Plantar: Upgoing
Autonomic: Postural hypotension

CNS
Spinal cord: Earliest locus of involvement
.....Major cause of sensory & motor disability
.....Posterior column fiber loss
.....Spasticity in legs
.....Similar clinical features to N2O toxicity

Other CNS
.....Cognitive impairment in adults: Leukoencephalopathy on MRI [JL note: ie. multifocal brain white matter inflammation]
.....Mental retardation or encephalopathy in childhood syndromes
.....Sensory: Reduced smell & taste
.....Gait ataxia

Anemia: Megaloblastic; Due to reduced DNA synthesis

Gastrointestinal: Glossitis; Diarrhea

Fingernails: Hyperpigmented

TESTING

Serum
Low B12
.....Clinically significant: < 100 pg/ml
.....Suspicious: < 200 pg/ml
High homocysteine & methymalonic acid
.....Confirm biological significance of low B12 levels

MRI
Hyperintense T2 lesions in posterior columns (50%)
Lesions resolve after 8 to 12 months of therapy

Evoked potentials
.....Somatosensory: Abnormal tibial & median
.....Motor: Normal in most

PATHOLOGY

Spinal cord
Multifocal axonal loss & demyelination
Localization
.....Cervical & thoracic
.....Posterior column > Anterolateral & Anterior

Peripheral nerve: Axonal loss; Occasional ± demyelination

TREATMENT: 1 mg i.m. q 3 months

PROGNOSIS: Stabilization, or Some improvement

Paresthesias
Resolve within weeks
Rarely transient exacerbation after treatment

Myelopathy changes slowly if at all

CAUSES OF B12 DEFICIENCY: Normal body stores last 3 to 4 years

Gastrointestinal malabsorption
Deficient intrinsic factor production
.....Post-gastrectomy
.....Antibody vs parietal cells: Pernicious anemia
........Onset: Median = 60 years; Female slightly > Male
........Antibody targets: Gastric H+/K+-ATPase
...........Catalytic α subunit, and
...........Glycoprotein β subunit
........Regions of stomach affected: Fundus & body; Not antrum
........Mechanisms of B12 deficiency
...........Reduced intrinsic factor production 2° parietal cell loss
...........Antibodies to B12 binding site on intrinsic factor: Prevent formation of complex that is normally carried to terminal ileum & absorbed
.......Associated immune disorders: Thyroiditis; Diabetes; Addison's; Ovarian failure; 1° hypoparathyroidism; Graves; Vitiligo; Myasthenia gravis; Lambert-Eaton syndrome; Common variable immunodeficiency with low Ig or IgA (younger patients)
.......Associated neoplasia: Gastric carcinoma (1% to 3%)
.......Family history: 20% of relatives also have pernicious anemia; Especially 1st degree females
.......Gastritis treatment: Corticosteroids; Azathioprine

No digestion of cobalamin-R-binder complex
Pancreatic insufficiency

Consumption of cobalamin in GI tract
Intestinal bacterial overgrowth

Poor absorption by distal ileum
Sprue-related disorders
Autosomal recessive disorders
Anemia; Proteinuria; Juvenile onset

Parasitic infection: Diphyllobothrium latum

Dietary inadequacy in vegetarians
Sources: Meat & dairy products

Congenital disorders of B12 binding proteins
Vitamin B12 R-binding protein deficiency
.....Neurological B12 deficiency syndromes in adults

Gastric intrinsic factor deficiency
.....Congenital anemia & jaundice

Transcobolamin II deficiency
.....Megaloblastic anemia; Diarrhea; Immunodeficiency; Mental retardation

Abnormalities of synthesis of active forms of B12
Methylcobalamin deficiency, types E and G
.....Neurological (CNS) & hematological B12 deficiency syndromes
.....In children

Adenosylcobalamin deficiency
.....Episodic ketoacidosis; Encephalopathy; Neutropenia; Osteoporosis

Combined methylcobalamin & adenosylcobalamin deficiency
.....Types I and II
.....Mental retardation; anemia; ± myelopathy in slowly progressive cases

Nitrous oxide exposure
.....Oxidizes cobalt in cobolamin: Methylcobalamin inactivated
.....Inhibits conversion of homocysteine to methionine:
.....Reduced supply of S-adenosylmethionine

Abnormal release of B12 from lysosomes

the main points are, take D3 not D2, and when you are having bloodwork done, the lab requisition should say 25(OH)vitaminD3 (or equivalent, i.e. 25-hydroxycholecalciferol. NOT 1,25 dihydroxycholecalciferol).