Spinal Cord Syndromes & Motor Neuron Disease

Upper vs Lower Motor Neuron Lesions

Two-neuron pathway. The upper motor neuron (UMN) descends from the motor cortex as the corticospinal or corticobulbar tract and synapses on the lower motor neuron (LMN) in the anterior horn or a cranial motor nucleus, whose axon runs through root and nerve to muscle.

Spinal shock. For hours to weeks after a severe cord injury, the limbs below the level are flaccid and areflexic and the bladder is atonic. Reflexes then return exaggerated, with spasticity, clonus, and Babinski signs; return of the bulbocavernosus reflex is an early marker that shock is ending. Neurogenic shock is a separate, hemodynamic problem: injuries above about T6 cut sympathetic outflow, causing hypotension with bradycardia.

LMN signs at the level of a cord lesion with UMN signs below it is the rule of cord localization; UMN and LMN signs in the same limb with normal sensation suggest ALS.

Incomplete Spinal Cord Syndromes

Anterior cord syndrome. The single anterior spinal artery supplies the anterior two-thirds of the cord. Infarction destroys the corticospinal tracts (bilateral paralysis below the level, spastic once spinal shock passes), the anterior horns (LMN weakness at the level), the spinothalamic tracts (bilateral pain and temperature loss), and autonomic fibers (bladder dysfunction). The dorsal columns, fed by the paired posterior spinal arteries, are spared, so vibration and proprioception stay normal.

Artery of Adamkiewicz. This great anterior radiculomedullary artery, usually arising on the left from an intercostal artery at T9–T12, is the main feeder of the anterior spinal artery for the lower cord. Aortic cross-clamping, thoracoabdominal aneurysm repair, or dissection can interrupt it and cause sudden paraplegia with urinary retention. The mid-thoracic cord (about T4–T8) is a watershed zone vulnerable to profound hypotension.

Central cord syndrome. The most common incomplete cord injury: an older adult with cervical spondylosis falls forward and hyperextends the neck. Central damage makes the arms, especially the hands, weaker than the legs, with urinary retention and variable sensory loss; hand function recovers least.

Cape-like sensory loss. Central lesions first cut spinothalamic fibers crossing in the anterior white commissure, giving bilateral cape-like loss of pain and temperature over the shoulders and arms with touch and vibration preserved. Syringomyelia, often with a Chiari I malformation, is the classic cause; painless hand burns are the clue, and an enlarging syrinx wastes the hand intrinsics (anterior horns) and makes the legs spastic (lateral corticospinal tracts).

Posterior cord syndrome. Dorsal column (fasciculus gracilis and cuneatus) damage removes vibration and joint-position sense below the lesion, causing sensory ataxia and a positive Romberg sign with strength and pain/temperature preserved. Causes include tabes dorsalis (neurosyphilis with lightning pains and Argyll Robertson pupils), compression, and nutritional myelopathy: B12 deficiency and nitrous oxide abuse (which oxidizes the cobalt in cobalamin) cause subacute combined degeneration with added corticospinal signs, and copper deficiency mimics it.

Conus Medullaris vs Cauda Equina

Anatomy. The adult cord ends as the conus medullaris at about L1–L2; below it, lumbosacral roots form the cauda equina, which is why lumbar puncture is done at L3–L4 or L4–L5. The conus holds the sacral segments for bladder, bowel, and sexual function and is ringed by exiting roots, so its lesions mix UMN and LMN findings.

New urinary retention, saddle anesthesia, or bilateral leg weakness with back pain demands emergency MRI; cauda equina compression is a surgical emergency, and outcome depends on prompt decompression.

Amyotrophic Lateral Sclerosis

Clinical picture. ALS is the most common adult motor neuron disease, usually beginning in the 50s or 60s with asymmetric limb weakness (clumsy hand, foot drop) or, in about a third, bulbar dysarthria and dysphagia. LMN signs (atrophy, fasciculations, cramps) coexist with UMN signs (spasticity, hyperreflexia, Babinski) in the same regions. Eye movements, sensation, and bladder/bowel sphincters (Onuf nucleus) are spared. Respiratory failure usually kills within 3–5 years; a subset develops frontotemporal dementia.

Pathology. "Amyotrophic" means neurogenic muscle atrophy from anterior horn cell loss; "lateral sclerosis" means gliosis of the lateral corticospinal tracts. Most cases show TDP-43-positive cytoplasmic inclusions, and EMG shows widespread denervation with normal sensory conduction.

Genetics. Familial ALS is usually autosomal dominant. A GGGGCC hexanucleotide repeat expansion in C9orf72 is the most common genetic cause of both familial ALS and frontotemporal dementia. SOD1 (copper-zinc superoxide dismutase, chromosome 21) mutations yield a misfolded enzyme that aggregates and promotes free-radical injury.

Treatment. Riluzole decreases presynaptic glutamate release, limiting excitotoxicity, and prolongs survival by a few months; liver enzymes are monitored. Edaravone, a free-radical scavenger, slows functional decline. Tofersen, an intrathecal antisense oligonucleotide that lowers SOD1, treats SOD1-associated ALS. Noninvasive ventilation prolongs survival, and gastrostomy maintains nutrition when swallowing fails.

Other Motor Neuron Disorders

ALS variants. Primary lateral sclerosis is pure UMN disease (slowly progressive spastic paraparesis and spastic dysarthria, with far longer survival); progressive muscular atrophy is pure LMN. Progressive bulbar palsy destroys the LMNs of cranial nerves IX, X, and XII, causing nasal dysarthria, dysphagia with aspiration, and a wasted, fasciculating tongue; many cases evolve into ALS.

Bulbar palsy is LMN (atrophic, fasciculating tongue; weak gag). Pseudobulbar palsy is bilateral corticobulbar UMN (small spastic tongue, brisk jaw jerk, involuntary laughing or crying).

Spinal muscular atrophy. Autosomal recessive loss of SMN1 on chromosome 5q, usually a homozygous exon 7 deletion, degenerates anterior horn cells. Infants have symmetric proximal weakness, hypotonia with frog-leg posture, tongue fasciculations, areflexia, and paradoxical breathing, with an alert face, normal cognition, and normal sensation. SMN2 transcripts mostly skip exon 7, so more SMN2 copies mean milder disease.

• Type 1 (Werdnig-Hoffmann): onset before 6 months; never sits.
• Type 2: onset 6–18 months; sits but never walks independently.
• Type 3 (Kugelberg-Welander): onset after 18 months; walks.

SMA therapy. Nusinersen, an intrathecal antisense oligonucleotide, promotes exon 7 inclusion in SMN2 transcripts; risdiplam is an oral SMN2 splicing modifier; onasemnogene abeparvovec is a one-time intravenous AAV9 vector carrying SMN1. Newborn screening allows presymptomatic treatment, when outcomes are best.

Poliomyelitis and West Nile virus. Poliovirus, a fecal-oral enterovirus, spreads from the gut to anterior horn cells in a small minority of infections: after a febrile illness, asymmetric flaccid paralysis with areflexia and atrophy develops while sensation stays normal, and CSF shows lymphocytic pleocytosis. Decades later, post-polio syndrome brings new fatigue and weakness as enlarged, reinnervated motor units fail. West Nile virus, a flavivirus spread by Culex mosquitoes from a bird reservoir, can cause encephalitis and the same polio-like flaccid paralysis, mainly in older or immunosuppressed adults.