Primary Lateral Sclerosis

Diseases, , ,

Diagnosis:

Clinical features plus unrevealing investigations (NCS/EMG, MRI, lab tests) for other causes. This  is a diagnosis of exclusion.
 

Diagnostic categories of PLS (Gordon et al.)

Autopsy-proven PLS

  • Clinically diagnosed PLS with degeneration in motor cortex and corticospinal tracts, no loss of motor neurons, no gliosis in anterior horn cells, and no Bunina bodies or ubiquinated inclusions.

Clinically pure PLS

  • Evident upper motor neuron signs, no focal muscle atrophy or visible fasciculations, and no evidence of denervation on EMG at 4 years from symptom onset. Age at onset after 40. Secondary and mimicking conditions excluded by laboratory and neuroimaging.

UMN-dominant ALS

  • Symptoms 4 years, or disability due predominately to UMN signs but with minor EMG denervation or LMN signs on examination that are not sufficient to meet diagnostic criteria for ALS.

PLS plus

  • Predominant UMN signs plus clinical, laboratory, or pathologic evidence of dementia, parkinsonism, or sensory tract abnormalities. (If cerebellar signs, urinary incontinence, or orthostatic hypotension are evident, multiple-system atrophy should be considered.)

Symptomatic lateral sclerosis

  • Clinically diagnosed PLS with evident possible cause (e.g., HIV infection, paraneoplastic syndrome).

Clinical features:

Erb’s triad: spasticity, hyperreflexia and mild weaknes. But also pseudobulbar affect, urinary dysfunction, asymptomatic eye movement abnormalities (saccadic breakdown
of smooth pursuit or supranuclear paralysis) and cognitive dysfunction.
This disease begins with spasticity followed by weakenss of the limbs and bulbar muscles.
Begins with leg symptoms that progresses bilaterally. Later on upper limb symptoms occurs followed by bulbar symptoms.
Symptoms are gradually progressive with spread from one leg to the next over 1-4 years, and to the hands in 1-6 years. Bulbar involvement occurs after an additional 0.5-5 years.
UMN features: spasticity, increased reflexes and up-going plantars
No sensory symptoms but mild abnomalities in SSEPs may occur

Findings on Investigations:

MRI brain and MRI spinal cord: atrophy of precentral gyrus, parietal cortex, and primary sensorimotor may occur.
NCS/EMG: electrophysiological evidence of mild denervation does not rule out the diagnosis
MEP, motor evoked potentials: abnormal, worse in the legs, absent MEP, or prolonged central conduction time 2-3 times upper limit of normal,
SSEP, somatosensory evoked potentials: may be prolonged
MRS: reduced N-acetylaspartate/creatine ratio, reduced N-acetylaspartate/creatine, reduced N-acetylaspartate/choline ratio,
DTI: decreased signal intensity in posterior limb of the internal capsule,
FDG-PET: decreased uptake and decreased regional CBF in precentral gyrus region,
Muscle biopsy: denervation or reinervation, minimal angular fibers,

Investigations to consider:

MRI brain and MRI spinal cord
NCS/EMG
Blood tests:

  • HTLV-1 testing
  • B12, RPR, HIV testing
  • Genetic testing for hereditary spastic paraparesis: SPG3A, SPG4, SPG6
  • Serum long-chain fatty acids: adrenomyeloneuropathy
  • CK: elevation can occur in 17-40% of patients

Testing for causes of myelopathy,
MEP, and SSEPs

Treatment:

Supportive care
Treatment of spasticity: baclofen or tizanidine
Treatment of pseudobulbar affect
Treatment of drooling:

  • Anticholinergics: benztropine mesylate, hycoscyamine, glycopyrrolate, or
    scopolamine patches
  • Botulinum toxin injection into salivary glands

Address pulmonary function
Multi-disceplinary supportive care:

  • Physical therapy, occupational therapy speech therapy, nutrition assessment
  • Social work, counselling

Related articles:

References:

  1. . Gordon PH, Cheng B, Katz IB, Pinto M, Hays AP, Mitsumoto H, et al. The natural history of primary lateral sclerosis. Neurology 2006;66:647– 653.
  2. Brooks BR. El Escorial World Federaton of Neurology criteria for the diagnosis of amyotrophic lateral sclerosis. J Neurol Sci 1994;124(suppl):96 –107.