eMedicine Specialties > Neurology > Neuromuscular Diseases

Primary Lateral Sclerosis: Differential Diagnoses & Workup

Author: Carmel Armon, MD, MSc, MHS, Professor of Neurology, Tufts University School of Medicine; Chief, Division of Neurology, Baystate Medical Center
Contributor Information and Disclosures

Updated: Jun 8, 2009

Differential Diagnoses

Amyotrophic Lateral Sclerosis
Multiple System Atrophy
Diffuse Sclerosis
Neurosyphilis
Glioblastoma Multiforme
Oligodendroglioma
HIV-1 Associated Opportunistic Infections: PML
Olivopontocerebellar Atrophy
HIV-1 Associated Opportunistic Neoplasms: CNS Lymphoma
Parkinson-Plus Syndromes
HIV-1 Associated Vacuolar Myelopathy
Prion-Related Diseases
Low-Grade Astrocytoma
Tropical Myeloneuropathies
Lyme Disease
Vitamin B-12 Associated Neurological Diseases
Meningioma
Multiple Sclerosis

Other Problems to Be Considered

Hereditary spastic paraparesis (HSP)
Konzo
Neurolathyrism
Spinocerebellar ataxias
Tumors of the spinal cord

Workup

Laboratory Studies

  • Laboratory studies for primary lateral sclerosis (PLS) should include hemogram, erythrocyte sedimentation rate, vitamin B-12 level, and, as indicated, Venereal Disease Research Laboratory (VDRL) (or rapid plasma reagent [RPR]), Lyme, HIV-1/HIV-2, and HTLV-1 serology tests.
  • Cerebrospinal fluid (CSF) analysis should include protein and glucose concentrations, cell count, and an MS panel.

Imaging Studies

  • MRI studies are obtained to exclude alternative diagnoses. MRI, MRS, SPECT, and PET changes have been described in some patients, but the usefulness of these studies in making the diagnosis early in the presentation of PLS is not known.
  • Similarly, diffusion tensor imaging and magnetization transfer imaging may provide insight into the pathophysiological process of amyotrophic lateral sclerosis (ALS) and PLS, by providing objective imaging evidence to support the clinical findings of upper motor neuron dysfunction. Further investigation is needed to determine and to compare the utility of various neuroimaging markers in making the diagnosis of PLS, in comparison to the clinical examination findings.
  • At this time, therefore, these advanced imaging techniques cannot be used alone to confirm or exclude the diagnosis of PLS.

Other Tests

  • Motor and sensory nerve conduction studies should be normal.
  • Needle EMG helps distinguish PLS from ALS by identifying, in ALS, electrophysiologic evidence of widespread lower motor neuron involvement. The changes in PLS are minimal or absent.
  • Repeat electrodiagnostic testing occasionally is needed to determine whether lower motor neurons are involved.
  • As overall activity diminishes, muscle atrophy may suggest lower motor neuron involvement. Such changes may be distinguished from muscle atrophy due to disuse secondary to upper motor neuron impairment on clinical grounds (eg, no fasciculations) and, more definitively, by electrophysiological testing. Occasionally, sparse, scattered, nonprogressive changes of denervation (ie, fibrillation potentials) may be seen in distal muscles.
  • Motor evoked potentials may show abnormalities of the upper motor neurons, but this test is not readily available in many centers.
  • Lower extremity somatosensory evoked potentials occasionally show prolonged latencies in patients with PLS, in the absence of sensory symptoms. This subclinical involvement of central sensory axons suggests that in those patients, the disease pathophysiology is not restricted to upper motor neurons, but rather affects them preferentially.
  • Genetic testing for HSP may be considered if the presentation and family history suggest the condition. Confirmation of a diagnosis of HSP results in an expectation for slower disease progression and a more limited range of clinical involvement and affects management of the patient. Appropriate genetic counseling should be offered to patients with suspected HSP before they are referred for genetic testing.

Procedures

A lumbar puncture should be considered to rule out other causes of spasticity (eg, MS) after appropriate imaging studies have been obtained.

Histologic Findings

See Pathophysiology.

More on Primary Lateral Sclerosis

Overview: Primary Lateral Sclerosis
Differential Diagnoses & Workup: Primary Lateral Sclerosis
Treatment & Medication: Primary Lateral Sclerosis
Follow-up: Primary Lateral Sclerosis
References
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References

  1. Younger DS, Chou S, Hays AP, et al. Primary lateral sclerosis. A clinical diagnosis reemerges. Arch Neurol. Dec 1988;45(12):1304-7. [Medline].

  2. Pringle CE, Hudson AJ, Munoz DG, et al. Primary lateral sclerosis. Clinical features, neuropathology and diagnostic criteria. Brain. Apr 1992;115 ( Pt 2):495-520. [Medline].

  3. Gordon PH, Cheng B, Katz IB, et al. The natural history of primary lateral sclerosis. Neurology. Mar 14 2006;66(5):647-53. [Medline].

  4. Tartaglia MC, Rowe A, Findlater K, Orange JB, Grace G, Strong MJ. Differentiation between primary lateral sclerosis and amyotrophic lateral sclerosis: examination of symptoms and signs at disease onset and during follow-up. Arch Neurol. Feb 2007;64(2):232-6. [Medline].

  5. Brugman F, Veldink JH, Franssen H, de Visser M, de Jong JM, Faber CG. Differentiation of hereditary spastic paraparesis from primary lateral sclerosis in sporadic adult-onset upper motor neuron syndromes. Arch Neurol. Apr 2009;66(4):509-14. [Medline].

  6. Panzeri C, De Palma C, Martinuzzi A, Daga A, De Polo G, Bresolin N. The first ALS2 missense mutation associated with JPLS reveals new aspects of alsin biological function. Brain. Jul 2006;129(Pt 7):1710-9. [Medline].

  7. Valdmanis PN, Dupré N, Rouleau GA. A locus for primary lateral sclerosis on chromosome 4ptel-4p16.1. Arch Neurol. Mar 2008;65(3):383-6. [Medline].

  8. Ciccarelli O, Behrens TE, Johansen-Berg H, Talbot K, Orrell RW, Howard RS. Investigation of white matter pathology in ALS and PLS using tract-based spatial statistics. Hum Brain Mapp. Feb 2009;30(2):615-24. [Medline].

  9. Stark FM, Moersch FP. Primary lateral sclerosis: a distinct clinical entity. J Nervous Mental Disease. 1945;102:332-337.

  10. Arruda WO, Coelho Neto M. Primary lateral sclerosis. A case report with SPECT study. Arq Neuropsiquiatr. Sep 1998;56(3A):465-71. [Medline].

  11. Beal MF, Richardson EP. Primary lateral sclerosis: a case report. Arch Neurol. Oct 1981;38(10):630-3. [Medline].

  12. Brown WF, Ebers GC, Hudson AJ, et al. Motor-evoked responses in primary lateral sclerosis. Muscle Nerve. May 1992;15(5):626-9. [Medline].

  13. Brugman F, Wokke JH, Vianney de Jong JM, et al. Primary lateral sclerosis as a phenotypic manifestation of familial ALS. Neurology. May 24 2005;64(10):1778-9. [Medline].

  14. Caliandro P, Pazzaglia C, Tonali P, Padua L. Diagnosis of multifocal motor neuropathy. Lancet Neurol. Jul 2005;4(7):393; author reply 393. [Medline].

  15. Chan S, Shungu DC, Douglas-Akinwande A, et al. Motor neuron diseases: comparison of single-voxel proton MR spectroscopy of the motor cortex with MR imaging of the brain. Radiology. Sep 1999;212(3):763-9. [Medline].

  16. Cruz Martinez A, Trejo JM. Transcranial magnetic stimulation in amyotrophic and primary lateral sclerosis. Electromyogr Clin Neurophysiol. Jul-Aug 1999;39(5):285-8. [Medline].

  17. Donaghy M. Classification and clinical features of motor neurone diseases and motor neuropathies in adults. J Neurol. May 1999;246(5):331-3. [Medline].

  18. Fisher CM. Pure spastic paralysis of corticospinal origin. Can J Neurol Sci. Nov 1977;4(4):251-8. [Medline].

  19. Gascon GG, Chavis P, Yaghmour A, et al. Familial childhood primary lateral sclerosis with associated gaze paresis. Neuropediatrics. Dec 1995;26(6):313-9. [Medline].

  20. Hudson AJ, Kiernan JA, Munoz DG. Clinicopathological features of primary lateral sclerosis are different from amyotrophic lateral sclerosis. Brain Res Bull. 1993;30(3-4):359-64. [Medline].

  21. Hudson AJ, Kiernan JA, Munoz DG, et al. Clinicopathological features of primary lateral sclerosis are different from amyotrophic lateral sclerosis. Brain Res Bull. 1993;30(3-4):359-64. [Medline].

  22. Lerman-Sagie T, Filiano J, Smith DW, Korson M. Infantile onset of hereditary ascending spastic paralysis with bulbar involvement. J Child Neurol. Jan 1996;11(1):54-7. [Medline].

  23. Milano JB, Neto MC, Hunhevicz SC, et al. Intrathecal baclofen for spasticity in primary lateral sclerosis. J Neurol. Jun 2005;252(6):740-1. [Medline].

  24. Park RM, Schulte PA, Bowman JD, et al. Potential occupational risks for neurodegenerative diseases. Am J Ind Med. Jul 2005;48(1):63-77. [Medline].

  25. Piquard A, Le Forestier N, Baudoin-Madec V, et al. Neuropsychological changes in patients with primary lateral sclerosis. Amyotroph Lateral Scler. Sep 2006;7(3):150-60. [Medline].

  26. Rowland LP. Primary lateral sclerosis, hereditary spastic paraplegia, and mutations in the alsin gene: historical background for the first International Conference. Amyotroph Lateral Scler Other Motor Neuron Disord. Jun 2005;6(2):67-76. [Medline].

  27. Strong MJ, Gordon PH. Primary lateral sclerosis, hereditary spastic paraplegia and amyotrophic lateral sclerosis: discrete entities or spectrum?. Amyotroph Lateral Scler Other Motor Neuron Disord. Mar 2005;6(1):8-16. [Medline].

  28. Wang S, Melhem ER. Amyotrophic lateral sclerosis and primary lateral sclerosis: The role of diffusion tensor imaging and other advanced MR-based techniques as objective upper motor neuron markers. Ann N Y Acad Sci. Dec 2005;1064:61-77. [Medline].

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Further Reading

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Keywords

PLS, motor neuron disease, motoneuron disease, progressive spasticity, stiffness, MNDs, primary lateral sclerosis, upper motor neurons, lower motor neurons, ALS, amyotrophic lateral sclerosis, progressive muscular atrophy, PMA, spinal muscular atrophies, SMAs, degenerative diseases

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Contributor Information and Disclosures

Author

Carmel Armon, MD, MSc, MHS, Professor of Neurology, Tufts University School of Medicine; Chief, Division of Neurology, Baystate Medical Center
Carmel Armon, MD, MSc, MHS is a member of the following medical societies: American Academy of Neurology, American Academy of Sleep Medicine, American Association of Neuromuscular and Electrodiagnostic Medicine, American Clinical Neurophysiology Society, American College of Physicians, American Epilepsy Society, American Medical Association, American Neurological Association, American Stroke Association, Massachusetts Medical Society, Movement Disorders Society, and Sigma Xi
Disclosure: Nothing to disclose.

Medical Editor

Paul E Barkhaus, MD, Professor, Department of Neurology, Medical College of Wisconsin; Director of Neuromuscular Diseases, Milwaukee Veterans Administration Medical Center
Paul E Barkhaus, MD is a member of the following medical societies: American Academy of Neurology, American Association of Neuromuscular and Electrodiagnostic Medicine, and American Neurological Association
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

Neil A Busis, MD, Chief, Division of Neurology, Department of Medicine, Head, Clinical Neurophysiology Laboratory, University of Pittsburgh Medical Center-Shadyside
Neil A Busis, MD is a member of the following medical societies: American Academy of Neurology and American Association of Neuromuscular and Electrodiagnostic Medicine
Disclosure: Nothing to disclose.

CME Editor

Selim R Benbadis, MD, Professor, Director of Comprehensive Epilepsy Program, Departments of Neurology and Neurosurgery, University of South Florida School of Medicine, Tampa General Hospital
Selim R Benbadis, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Sleep Medicine, American Clinical Neurophysiology Society, American Epilepsy Society, and American Medical Association
Disclosure: Nothing to disclose.

Chief Editor

Nicholas Y Lorenzo, MD, Chief Editor, eMedicine Neurology; Consulting Staff, Neurology Specialists and Consultants
Nicholas Y Lorenzo, MD is a member of the following medical societies: Alpha Omega Alpha and American Academy of Neurology
Disclosure: Nothing to disclose.

 
 
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