Metabolic
(Subacute) combined system disease (CSD)
- B12 deficiency causing posterior column myelopathy
- AKA
- subacute combined columnal degeneration
- Due to vitamin B12 (cyanocobalamin) deficiency
- Vitamin B12
- is a water soluble vitamin found in meats and dairy products.
- Its absorption in the distal duodenum is facilitated by intrinsic factor, a small polypeptide secreted by gastric parietal cells.
- Function
- Neurologic function
- Production of RBCs
- DNA synthesis
- Conversion of methylmalonic acid to succinyl coenzyme A
- Conversion of homocysteine to methionine
- Aetiologies of vitamin B12 deficiency:
- Dietary deficiency of B12:
- non meat-eaters may have insufficient intake.
- Chronic autoimmune gastritis:
- reduces available intrinsic factor which leads to intestinal malabsorption of B12 in the distal ileum
- Other gastric disorders:
- low gastric pH, e.g. in Zollinger-Ellison syndrome, can inhibit attachment of intrinsic factor to ileal receptors
- Chronic use of metformin (> 4 months), proton pump inhibitors (> 12 months) or histamine H2 blockers (> 12 months)
- Clinical features:
- Pernicious Anaemia:
- a macrocytic megaloblastic anemia
- Combined system disease (CSD):
- myelopathy involving primarily the posterior columns.
- Onset is gradual and uniform.
- Begins with symmetrical paresthesias in feet or hands (posterior column involvement) → leg stiffness, weakness, and proprioceptive deficits with unsteadiness that is worse in the dark → spasticity → paraplegia → bowel and bladder dysfunction.
- Dementia (confusion, memory impairment, irritability…) occurs in advanced cases due to cerebral white matter changes.
- Visual disturbances with or without optic atrophy may be due to optic nerve demyelination
- Labs:
- CBC:
- most (but not all) patients will have a macrocytic (megalocytic) anemia (folic acid deficiency also produces megaloblastic anemia.
- Folic acid corrects the anemia, even with CSD, but not the neurologic deficits which may actually worsen)
- Serum vitamin B12 (cobalamin):
- levels < 150 pg/ml are diagnostic.
- However, normal B12 levels do not R/O B12 deficiency
- if B12 levels are low, or if they are normal but the patient has macrocytic anemia or neurologic symptoms, then check for elevated serum methylmalonic acid (also check homocysteine to R/O folate deficiency)
- Schilling test:
- determines the cause of the B12 deficiency even if B12 injections have already been given
- (radiolabeled cyanocobalamin is given orally, followed by a parenteral flushing dose of nonradioactive vitamin, and the percentage of radioactivity is measured in the urine over 24 hours, performed once without and then once with added intrinsic factor, and then once following antibiotic therapy)
- Imaging:
- T2WI MRI may demonstrate increased signal within the white matter of the spinal cord, predominantly in the posterior columns but may also be seen in spinothalamic tracts
- Treatment:
- B12 injections q 1–3 months or large doses of oral preparations (other transport systems independent of intrinsic factor results in absorption of ≈ 1% of orally administered B12, doses of 300–100,000 mcg result in absorption of more than the daily requirement of 1–2.5 mcg)
ALS
Feature | ALS (Amyotrophic Lateral Sclerosis) | CSM (Cervical Spondylotic Myelopathy) |
Cause | Progressive neurodegenerative disease of upper and lower motor neurons | Chronic, non-traumatic, progressive cervical cord compression due to degenerative spine disease |
Clinical Course | Fatal, progressive; most die within 2 years of diagnosis | Progressive; treatable; requires surgery in moderate-severe cases |
Motor Symptoms | Weakness, atrophy, fasciculations, spasticity, upper & lower motor neuron signs | Weakness, clumsiness, atrophy, hyperreflexia, spasticity; upper motor neuron signs predominate (anterior horn involvement possible) |
Bulbar/Cranial Nerve & Cognitive Involvement | Bulbar signs common: dysarthria, dysphagia, tongue atrophy/fasciculations; up to 50% may exhibit cognitive (especially executive) dysfunction or frontotemporal dementia | No bulbar or cognitive involvement |
Sensory Symptoms | Absent | Sensory changes common (paresthesia, numbness) Pure motor forms ("cervical spondylotic amyotrophy") exist and mimic ALS |
Diagnostic “Red Flags” | Bulbar/cognitive/behavioral symptoms Rapidly progressive weakness Split-hand atrophy Tongue fasciculations Absence of marked sensory or sphincter signs | Sensory level on exam Typical radiological finding Sphincter dysfunction Absence of bulbar/cognitive features Improvement or stabilization with surgery |
Sphincter Dysfunction | Rare in ALS; points against diagnosis if present | Early or significant sphincter dysfunction points toward CSM |
EMG/Neurophysiology | Shows widespread denervation (fibrillations, sharp waves), both upper and lower motor neuron features, including unaffected limbs; lower motor neuron degeneration in areas without clinical deficit | Abnormalities confined to compressed spinal segments; EMG and nerve conduction can help exclude ALS and peripheral neuropathies. Special EMG differences: e.g., ulnar/median CMAP ratios, repetitive stimulation more abnormal in ALS; "split hand" and MUNIX tests helpful |
Imaging | MRI is normal or shows only muscle atrophy; does not show cord compression | MRI: confirms cord compression (criteria needed for diagnosis); important as imaging alone may not rule out ALS—must correlate with symptoms |
Prognosis | Invariably progressive; no disease-modifying cure available | Potential for stabilization or improvement post-surgery; surgical treatment indicated as disease progresses |
Treatment | Supportive, multidisciplinary; manage symptoms, maintain nutrition and respiration; surgery not beneficial (may even cause diagnostic delay or iatrogenic intervention) | Physical therapy, immobilization, anti-inflammatories, removal of high-impact activities, followed by surgery (anterior or posterior approach, depending on case) for moderate-severe or progressive disease |
Misdiagnosis/Overlap Issues | Very high risk of being misdiagnosed as CSM (CSM is the most common neurologist-made misdiagnosis in ALS); up to 14% undergoes unnecessary surgery; imaging and clinical "red flags" are critical for correct differentiation | CSM can have pure motor forms that closely resemble ALS ("CSA"); when ALS and CSM co-exist, surgical outcomes are poor, and improvement is rare; careful clinical and neurophysiological assessment required |
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