Acute non-traumatic tetraparesis – Differential diagnosis

  • Author Footnotes
    1 ORCID: 0000-0003-1181-1418.
    Renato Oliveira
    Corresponding author at: Hospital da Luz - Lisboa, Avenida Lusíada 100, 1500-650 Lisbon, Portugal.
    1 ORCID: 0000-0003-1181-1418.
    Department of Neurology, Hospital da Luz Lisboa, Lisbon, Portugal

    Department of Neurology, Department of Neurosciences and Mental Health, Hospital de Santa Maria, Centro Hospitalar Universitário Lisboa Norte, Lisbon, Portugal

    CHRC Comprehensive Health Research Centre, Universidade Nova de Lisboa, Lisbon, Portugal
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  • Filipa Ramalho Rocha
    Department of Internal Medicine, Hospital da Luz Lisboa, Lisbon, Portugal
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  • Tomás Teodoro
    CHRC Comprehensive Health Research Centre, Universidade Nova de Lisboa, Lisbon, Portugal

    Department of Psychiatry, Centro Hospitalar Psiquiátrico de Lisboa, Lisbon, Portugal
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  • Miguel Oliveira Santos
    Department of Neurology, Hospital da Luz Lisboa, Lisbon, Portugal

    Department of Neurology, Department of Neurosciences and Mental Health, Hospital de Santa Maria, Centro Hospitalar Universitário Lisboa Norte, Lisbon, Portugal

    Institute of Physiology, Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Lisbon, Portugal
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  • Author Footnotes
    1 ORCID: 0000-0003-1181-1418.


      • Acute tetraparesis is a debilitating and sometimes life-threatening condition.
      • History and examination are essential in establishing the correct diagnosis.
      • A practical approach is to use the neuroaxis as an anatomical guide.
      • Updated information on new neurological entities and treatments are also mentioned.



      Potentially life-threatening disorders may present in the emergency department with acute tetraparesis, and their recognition is crucial for an appropriate management and timely treatment. Our review aims to systematize the differential diagnosis of acute non-traumatic tetraparesis.


      Causes of tetraparesis can be classified based on the site of defect: upper motor neuron (UMN), peripheral nerve, neuromuscular junction or muscle. History of present illness should include the distribution of weakness (symmetric/asymmetric or distal/proximal/diffuse) and associated clinical features (pain, sensory findings, dysautonomia, and cranial nerve abnormalities such as diplopia and dysphagia). Neurological examination, particularly tendon reflexes, helps further in the localization of nerve lesions and distinction between UMN and lower motor neuron. Ancillary studies include blood and cerebral spinal fluid analysis, neuroaxis imaging, electromyography, muscle magnetic resonance and muscle biopsy.


      Acute tetraparesis is still a debilitating and potentially serious neurological condition. Despite all the supplementary ancillary tests, the neurological examination is the key to achieve a correct diagnosis. The identification of life-threatening neurologic disorders is pivotal, since failing to identify patients at risk of complications, such as acute respiratory failure, may have catastrophic results.


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      1. Ropper AH, Adams RD, Samuels MA, Victor M. Adams and Victor’s Principles of Neurology. McGraw-Hill Education LLC.; 2009. Accessed March 26, 2020.

        • Ganti L.
        • Rastogi V.
        Acute generalized weakness.
        Emerg Med Clin North Am. 2016; 34: 795-809
        • Nickel C.H.
        • Nemec M.
        • Bingisser R.
        Weakness as presenting symptom in the emergency department.
        Swiss Med Wkly. 2009; 139 (smw-12620): 271-272
        • Bingisser R.
        • Dietrich M.
        • Nieves Ortega R.
        • Malinovska A.
        • Bosia T.
        • Nickel C.H.
        Systematically assessed symptoms as outcome predictors in emergency patients.
        Eur J Internal Med. 2017; 45: 8-12
        • Spitzer A.R.
        • Giancarlo T.
        • Maher L.
        • Awerbuch G.
        • Bowles A.
        Neuromuscular causes of prolonged ventilator dependency.
        Muscle Nerve. 1992; 15: 682-686
        • Nayak R.
        Practical approach to the patient with acute neuromuscular weakness.
        WJCC. 2017; 5: 270
        • Hutchinson D.
        • Whyte K.
        Neuromuscular disease and respiratory failure.
        Practical Neurol. 2008; 8: 229-237
      2. Shah SM, Kelly KM. Principles and practice of emergency neurology: handbook for emergency physicians. Cambridge University Press; 2003. Accessed March 27, 2020.

        • Dimachkie M.M.
        • Barohn R.J.
        Guillain-Barré syndrome and variants.
        Neurol Clin. 2013; 31: 491-510
        • Al-bassam W.
        • Kubicki M.
        • Bailey M.
        • et al.
        Characteristics, incidence, and outcome of patients admitted to the intensive care unit with myasthenia gravis.
        J Crit Care. 2018; 45: 90-94
        • Lahiri S.
        • Mayer S.A.
        • Fink M.E.
        • et al.
        Mechanical ventilation for acute stroke: a multi-state population-based study.
        Neurocrit Care. 2015; 23: 28-32
        • Zantah M.
        • Coyle T.B.
        • Datta D.
        Acute respiratory failure due to neuromyelitis optica treated successfully with plasmapheresis.
        Case Rep Pulmonol. 2016; 2016: 1-3
        • Maramattom B.V.
        • Wijdicks E.F.M.
        Acute neuromuscular weakness in the intensive care unit.
        Crit Care Med. 2006; 34: 2835-2841
      3. Katirji B. Electromyography in clinical practice. 2007.

        • Gilhus N.E.
        • Tzartos S.
        • Evoli A.
        Myasthenia gravis.
        Nature. 2019; 5
        • Flower O.
        • Bowles C.
        • Wijdicks E.
        • Weingart S.D.
        • Smith W.S.
        Emergency neurological life support: acute non-traumatic weakness.
        Neurocrit Care. 2012; 17: 79-95
      4. Emos MC, Agarwal S. Neuroanatomy, Upper motor neuron Lesion. In: StatPearls. StatPearls Publishing; 2020. Accessed April 9, 2020.

        • Jeyakumar N.
        • Etchegaray M.
        • Henry J.
        • et al.
        The terrible triad of checkpoint inhibition: a case report of myasthenia gravis, myocarditis, and myositis induced by cemiplimab in a patient with metastatic cutaneous squamous cell carcinoma.
        Case Rep Immunol. 2020; 2020: 1-4
        • Gutmann L.
        • Gutmann L.
        Myokymia and neuromyotonia2004.
        J Neurol. 2004; 251: 138-142
        • Caplan L.R.
        Caplan’s stroke: a clinical approach.
        4th ed. Elsevier/Saunders, 2009
        • Mariano R.
        • Flanagan E.P.
        • Weinshenker B.G.
        • Palace J.
        A practical approach to the diagnosis of spinal cord lesions.
        Pract Neurol. 2018; 18: 187-200
        • Barohn R.J.
        • Dimachkie M.M.
        • Jackson C.E.
        A pattern recognition approach to the patient with a suspected myopathy.
        Neurol Clin. 2014; 32 (569–vii)
        • Saleh C.
        • Michel-de Cazotte E.
        • Hund-Georgiadis M.
        Tetraparesis following an Anterior Circulation Stroke: A Case Report.
        Case Rep Neurol. 2018; 10: 342-345
      5. Pinto WBV de R, Souza PVS de, Albuquerque MVC de, Dutra LA, Pedroso JL, Barsottini OGP. Clinical and epidemiological profiles of non-traumatic myelopathies. Arq Neuro-Psiquiatr. 2016;74(2):161-165. 10.1590/0004-282X20160001.

        • Grahn A.
        • Studahl M.
        Varicella-zoster virus infections of the central nervous system – Prognosis, diagnostics and treatment.
        J Infect. 2015; 71: 281-293
        • Bruscolini A.
        • Sacchetti M.
        • La Cava M.
        • et al.
        Diagnosis and management of neuromyelitis optica spectrum disorders - An update.
        Autoimmun Rev. 2018; 17: 195-200
        • New P.W.
        • Biering-Sørensen F.
        Review of the history of non-traumatic spinal cord dysfunction.
        Top Spinal Cord Injury Rehabilitation. 2017; 23: 285-298
        • de Seze J.
        Acute myelopathies: clinical, laboratory and outcome profiles in 79 cases.
        Brain. 2001; 124: 1509-1521
        • Leonhard S.E.
        • et al.
        Diagnosis and management of Guillain-Barré syndrome in ten steps.
        Nat Rev|Neurol. 2019; 15: 671-683
        • Mehndiratta M.M.
        • Mehndiratta P.
        • Pande R.
        Poliomyelitis: historical facts, epidemiology, and current challenges in eradication.
        Neurohospitalist. 2014; 4: 223-229
        • Russell J.A.
        General approach to peripheral nerve disorders.
        Continuum Am Acad Neurol. 2017; 23: 1241-1262
        • Chung T.
        • Prasad l.
        • Lloyd T.E.
        Peripheral neuropathy – clinical and electrophysiological considerations.
        Neuroimaging Clin N Am. 2014; 24: 49-65
        • Donofrio P.D.
        Guillain-Barre Syndrome.
        Continuum, Am Acad Neurol. 2017; 23: 1295-1309
        • Uncini A.
        • Kuwabara S.
        The electrodiagnosis of Guillain-Barré syndrome subtypes: Where do we stand?.
        Clin Neurophysiol. 2018; 129: 2586-2593
        • Uncini A.
        • Vallat J.-M.
        Autoimmune nodo-paranodopathies of peripheral nerve: the concept is gaining ground.
        J Neurol Neurosurg Psychiatry. 2018; 89: 627-635
        • Uncini A.
        • Ippoliti L.
        • Shahrizaila N.
        • Sekiguchi Y.
        • Kuwabara S.
        Optimizing the electrodiagnostic accuracy in Guillain-Barré syndrome subtypes: criteria sets and sparse linear discriminant analysis.
        Clin Neurophysiol. 2017; 128: 1176-1183
        • Grimm A.
        • Oertl H.
        • Auffenberg E.
        • et al.
        Differentiation between Guillain-Barré syndrome and acute-onset chronic inflammatory demyelinating polyradiculoneuritis—a prospective follow-up study using ultrasound and neurophysiological measurements.
        Neurotherapeutics. 2019; 16: 838-847
        • Shepherd S.
        • Batra A.
        • Lerner D.P.
        Review of critical illness myopathy and neuropathy.
        Neurohospitalist. 2017; 7: 41-48
        • Bryan Young G.
        • Hammond R.R.
        A stronger approach to weakness in the intensive care unit.
        Crit Care. 2004; 8: 416-418
        • Zhou C.
        • Wu L.
        • Ni F.
        • Ji W.
        • Wu J.
        • Zhang H.
        Critical illness polyneuropathy and myopathy: a systematic review.
        Neural Regen Res. 2014; 9: 101-110
        • Stölzel U.
        • Doss M.O.
        • Schuppan D.
        Clinical guide and update on porphyrias.
        Gastroenterology. 2019; 157: 365-381
      6. Jennifer A. Tracy, P. James B. Dyck. Porphyria and its neurologic manifestations. In: Handbook of clinical neurology. Vol 120. Neurologic Aspects of Systemic Disease Part II. Elsevier; 2014.

        • Suh Y.
        • Gandhi J.
        • Seyam O.
        • Jiang W.
        • Joshi G.
        • Smith N.
        • Khan S.A.
        Neurological and neuropsychiatric manifestations of porphyria.
        Int J Neurosci. 2019;
        • Rigora J.
        • Pintoa S.A.
        • Martins-Mendesa D.
        Porphyrias: A clinically based approach.
        Eur J Internal Med. 2019; 67: 24-29
      7. L.J. Scott. Givosiran: First Approval. Drugs, Springer Nature Switzerland AG. Published online 2020. https :// are.11741 715.

        • Ratnaike R.N.
        Acute and chronic arsenic toxicity.
        Postgrad Med J. 2003; 79: 391-396
      8. Ganti & Rastogi. Acute generalized weakness. Emerg Med Clin N Am. Published online 2016.

        • Nayak R.
        Practical approach to the patient with acute neuromuscular weakness.
        World J Clin Cases. 2017; 5: 270-280
        • Pasnoor M.
        • Dimachkie M.M.
        Approach to muscle and neuromuscular junction disorders.
        Continuum (Minneap Minn). 2019; 25: 536-1563
        • Tanboon J.
        • Nishino I.
        Classification of idiopathic inflammatory myopathies: pathology perspectives.
        Curr Opin Neurol. 2019; 32: 704-714
      9. N.A. Goyal, Immune-mediated myopathies. Continuum (Minneap Minn). 2019;25(6):1564–1585.

      10. R.W. Orrell. Endocrine myopathies. In: Handbook of Clinical Neurology. Vol 86. 3rd series. Elsevier; 2007.

        • Chawla J.
        Stepwise approach to myopathy in systemic disease.
        Front Neurol. 2011; 2: 1-10
        • Statland J.M.
        • Fontaine B.
        • Hanna M.G.
        • et al.
        Review of the diagnosis and treatment of periodic paralysis.
        Muscle Nerve. 2018; 57: 522-530
      11. Doughty CT, Amato AA. Toxic myopathies. Continuum (Minneap Minn). 25(6):1712–1731.

        • Teodoro T.
        • Edwards M.J.
        • Isaacs J.D.
        A unifying theory for cognitive abnormalities in functional neurological disorders, fibromyalgia and chronic fatigue syndrome: systematic review.
        J Neurol Neurosurg Psychiatry. 2018; 89: 1308-1319
        • Roelofs J.J.
        • Teodoro T.
        • Edwards M.J.
        Neuroimaging in functional movement disorders.
        Curr Neurol Neurosci Rep. 2019; 19: 12
        • Teodoro T.
        • Edwards M.J.
        Functional movement disorders.
        Curr Opin Neurol. 2016; 29: 519-525
        • Longarzo M.
        • Cavaliere C.
        • Mele G.
        • et al.
        Microstructural changes in motor functional conversion disorder: multimodal imaging approach on a case.
        Brain Sci. 2020; 10: 385