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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Fahimeh Shojaei, M.D. Julinka Auta Fernandes

Overview

Physical examination of patients with multiple sclerosis (MS) may demonstrate objective abnormalities involving the visual, brainstem, pyramidal, cerebellar, sensory, gait, cognitive, and autonomic systems. Common findings include internuclear ophthalmoplegia, optic nerve involvement/optic neuritis, nystagmus, spasticity, hyperreflexia, pathological plantar responses, weakness, sensory deficits, tremor, dysmetria, Lhermitte's sign, and gait or balance impairment. Bladder, bowel, sexual, and cognitive symptoms should also be assessed because they may not be apparent from the routine neurological examination alone.

The neurological examination should be interpreted together with the clinical history and appropriate paraclinical investigations, while alternative explanations for the presentation are considered. The 2024 McDonald criteria recognize the optic nerve as a fifth anatomical location for multiple sclerosis, in addition to periventricular, juxtacortical/cortical, infratentorial, and spinal cord locations.

Because the revised diagnostic criteria incorporate clinical, imaging, and laboratory evidence, examination findings should be interpreted in the context of the complete clinical presentation and potential alternative diagnoses to minimize misdiagnosis.

Physical Examination

Physical examination of patients with multiple sclerosis should be systematic and should document objective neurological abnormalities, functional impairment, and relevant non-neurological findings. The examination should be interpreted together with the clinical history and appropriate paraclinical testing.

Appearance of the Patient

• Gait and balance disturbance: Observe gait initiation, base, stride, turning, foot clearance, arm swing, use of assistive devices, and ability to perform tandem gait. Gait impairment may result from pyramidal weakness or spasticity, cerebellar dysfunction, sensory impairment, vestibular dysfunction, or combinations of these abnormalities.
• Falls and postural instability should be assessed when clinically indicated.
• The Timed 25-Foot Walk Test (T25FW) may be used to quantify ambulatory performance and for longitudinal assessment of walking function in multiple sclerosis.

Vital Signs

• Routine vital signs are generally normal unless there is comorbidity or associated autonomic dysfunction.
• Blood pressure and heart rate should be assessed as clinically indicated. Symptoms suggestive of orthostatic intolerance may warrant assessment of orthostatic vital signs.

Skin

• Skin examination of patients with multiple sclerosis is usually normal.
• Assess for pressure injury, skin breakdown, or other complications in patients with significant immobility or impaired sensation.

HEENT

• Internuclear ophthalmoplegia (INO): INO results from involvement of the medial longitudinal fasciculus and is characterized by impaired adduction of the ipsilateral eye during lateral gaze, often accompanied by abducting nystagmus of the contralateral eye. Ocular alignment and extraocular movements should be examined systematically.

• Optic neuritis/optic nerve involvement:
  • Assess visual acuity in each eye separately.
  • Assess color vision when appropriate using a standardized color-vision test.
  • Assess the pupillary light reflex and look for a relative afferent pupillary defect (RAPD) when unilateral or asymmetric optic nerve dysfunction is suspected.
  • Assess visual fields when clinically indicated.
  • Perform fundoscopy to assess the optic disc and retina. A normal funduscopic examination does not exclude retrobulbar optic neuritis.
  • Optic neuritis may be an initial manifestation of multiple sclerosis and should be evaluated in the context of the complete neurological examination and appropriate imaging.
  • Optical coherence tomography (OCT) and visual evoked potential (VEP) are paraclinical investigations rather than components of the bedside physical examination. When appropriately performed and interpreted, they may provide supportive evidence of optic nerve injury or demyelinating optic nerve involvement when there is no better explanation.

• Nystagmus
• Diplopia
• Extra-ocular movements may be abnormal
• Facial sensory symptoms or facial pain may occur depending on the site of CNS involvement.
• Prominent hearing loss is uncommon in multiple sclerosis and should prompt consideration of alternative or additional diagnoses.

Neck

• Neck examination is often normal.
• Assess cervical range of motion and neurological signs when Lhermitte's sign or suspected cervical spinal cord involvement is present.

Lungs

• Pulmonary examination is usually normal.
• Assess respiratory function when there is advanced disability, severe weakness, bulbar dysfunction, or concern for respiratory compromise.

Heart

• Cardiovascular examination is usually normal.
• Evaluate for orthostatic symptoms or cardiovascular comorbidity when clinically indicated.

Abdomen

• Abdominal examination is usually normal.
• Abdominal examination may be relevant when evaluating bowel dysfunction, constipation, abdominal pain, or other abdominal symptoms.

Back

• Back examination is usually normal.
• Assess the cervical and thoracic spine when spinal cord symptoms, sensory levels, weakness, or Lhermitte's sign are present.

Genitourinary

• Lower urinary tract symptoms may include urinary urgency, frequency, nocturia, hesitancy, retention, incomplete emptying, or urinary incontinence.
• Patients with urinary symptoms should have directed history and physical examination. Post-void residual (PVR) urine volume should be measured when urinary symptoms change or when retention or incomplete emptying is suspected.
• Erectile dysfunction and other sexual dysfunction may occur.
• Vaginal dryness, reduced genital sensation, dyspareunia, and other sexual symptoms may occur.
• Bowel dysfunction, including constipation or fecal urgency/incontinence, should be assessed when clinically relevant.

Neuromuscular

• Lhermitte's sign: An electric-shock-like sensation radiating down the spine or into the limbs may be reported or elicited with neck flexion. It is associated with cervical spinal cord or cervicomedullary involvement and is a supportive clinical finding rather than a specific diagnostic sign.

• Spasticity: Examine passive range of motion and velocity-dependent increase in muscle tone, particularly in the lower extremities. Standardized scales such as the Modified Ashworth Scale may be used when quantitative documentation of spasticity is required.

• Muscle strength should be assessed systematically and documented using a standardized grading system such as the Medical Research Council (MRC) scale.
• Hyperreflexia
• Clonus
• Positive (abnormal) Babinski response or other extensor plantar response
• Proximal and/or distal muscle weakness, unilateral or bilateral
• Sensory loss involving the face, trunk, or upper/lower extremities
• Assess superficial and deep sensation, including light touch, pinprick, vibration, and proprioception as clinically appropriate.
• Assess for a sensory level when spinal cord involvement is suspected.
• Abnormal gait
• Positive Trendelenburg sign when hip abductor weakness is present
• Tremor
• Dysmetria
• Dysdiadochokinesia or impaired rapid alternating movements
• Finger-to-nose and heel-to-shin testing should be performed when cerebellar dysfunction is suspected.
• Assess for intention tremor, truncal ataxia, and impaired coordination.

Cognitive and Behavioral Examination

• Cognitive impairment may occur in multiple sclerosis and may not be detected by routine orientation testing alone.
• Assess attention, processing speed, executive function, memory, language, and visuospatial function when clinically indicated.
• The Symbol Digit Modalities Test (SDMT) or another validated cognitive screening instrument may be used for baseline and longitudinal assessment in clinically stable patients with multiple sclerosis. The National Multiple Sclerosis Society recommendations were endorsed by the Consortium of Multiple Sclerosis Centers and the International Multiple Sclerosis Cognition Society.
• More comprehensive neuropsychological assessment should be considered when screening is abnormal, cognitive decline is suspected, or cognitive symptoms interfere with daily functioning.

Functional Assessment

• Timed 25-Foot Walk Test may be used to quantify walking performance and for longitudinal assessment.
• The Nine-Hole Peg Test may be used to assess upper-extremity manual dexterity when a standardized functional assessment is required.
• The Expanded Disability Status Scale (EDSS) may be used to quantify overall neurological disability. EDSS incorporates standardized assessment of neurological functional systems and ambulation and should complement, rather than replace, a detailed neurological examination.

Diagnostic and Paraclinical Correlation

• The neurological examination should be integrated with MRI and other appropriate investigations rather than interpreted in isolation.
• The 2024 McDonald criteria recognize five anatomical locations relevant to dissemination in space: periventricular, juxtacortical/cortical, infratentorial, spinal cord, and optic nerve.
• The 2024 MAGNIMS-CMSC-NAIMS consensus recommendations provide updated guidance on MRI acquisition and interpretation for MS diagnosis, including appropriate assessment of the brain, spinal cord, and optic nerve. Brain and spinal cord imaging should be performed as part of diagnostic assessment, with appropriate sequences for detection of symptomatic optic nerve lesions and susceptibility-sensitive sequences for evaluation of the central vein sign and paramagnetic rim lesions when indicated.
• The central vein sign and paramagnetic rim lesions are supportive MRI biomarkers in selected diagnostic situations; they are not physical-examination findings.
• Kappa free light chains in cerebrospinal fluid may provide supportive diagnostic evidence in selected situations and should be regarded as a laboratory biomarker rather than a physical-examination finding.
• When optic nerve involvement is suspected but clinical findings are equivocal, optic-nerve MRI, OCT, or VEP may provide supportive evidence as appropriate. OCT-derived retinal nerve fibre layer or macular ganglion-cell measures may support optic nerve injury when appropriate quality control is applied and there is no better explanation. Delayed VEP latency may support demyelinating optic nerve injury, but interpretation is centre- and device-dependent and requires appropriate technical expertise.
• When the clinical presentation is atypical, particularly in older adults or patients with relevant comorbidities, clinicians should maintain a broad differential diagnosis and exclude alternative explanations before assigning a diagnosis of multiple sclerosis.
• Implementation of the revised McDonald criteria requires appropriate access to advanced imaging, standardized laboratory testing, multidisciplinary expertise, and careful clinical judgment to minimize misdiagnosis and support equitable access to diagnostic evaluation.

Recent Discussion of the Revised Diagnostic Criteria

• The 2024 McDonald criteria have generated published discussion regarding the balance between earlier diagnosis and maintaining diagnostic specificity. These publications represent expert commentary and implementation considerations rather than replacement of the 2024 McDonald criteria.