What are the key components of a complete central nervous system (CNS) examination and differential diagnosis?

Complete CNS Examination and Differential Diagnosis

Mental Status Examination

Begin by assessing level of consciousness, orientation, attention, memory, language, and executive function using validated tools whenever possible. 1

• Evaluate cognitive domains systematically: attention/concentration, memory (immediate, short-term, long-term), language (naming, comprehension, repetition), visuospatial function, and executive function (planning, judgment, abstract reasoning). 1
• Assess for behavioral changes: apathy, disinhibition, loss of empathy, compulsive behaviors, and changes in personality that may indicate frontotemporal pathology. 1
• Screen for mood disorders: depression, anxiety, and psychosis using structured scales when feasible (e.g., Geriatric Depression Scale, Neuropsychiatric Inventory). 1
• Evaluate insight and awareness: patients with neurodegenerative disease, particularly frontotemporal dementia, often lack insight into their deficits more than those with psychiatric disorders. 1

Cranial Nerve Examination

Systematically test all 12 cranial nerves, paying particular attention to patterns that localize lesions. 1, 2

CN I (Olfactory)

• Test each nostril separately with familiar odors (coffee, vanilla); anosmia may indicate frontal lobe pathology or COVID-19 sequelae. 2

CN II (Optic)

• Visual acuity: test each eye separately with Snellen chart or near card. 1
• Visual fields: confrontation testing in all four quadrants bilaterally. 1
• Fundoscopy: assess optic disc, vessels, and retina; red reflexes should be detectable and symmetric. 1
• Pupillary light reflex: direct and consensual responses. 1

CN III, IV, VI (Oculomotor, Trochlear, Abducens)

• Extraocular movements: test in all directions (H-pattern); note any diplopia, nystagmus, or limitation. 1, 2
• Pupil size and reactivity: CN III palsy causes pupillary dilation and ptosis. 3, 4
• Ptosis assessment: CN III palsy causes eyelid drooping; CN VI palsy does NOT cause ptosis. 4
• Eye position at rest: CN III palsy shows "down and out" position; CN VI palsy shows esotropia (eye turned inward). 4
• Saccade velocity: decreased velocity suggests progressive supranuclear palsy or frontotemporal dementia. 1

CN V (Trigeminal)

• Sensory: light touch and pinprick in all three divisions (V1, V2, V3) bilaterally. 2
• Motor: palpate masseter and temporalis muscles during jaw clenching; test jaw opening against resistance. 2
• Corneal reflex: if indicated (afferent CN V, efferent CN VII). 2

CN VII (Facial)

• Motor function: observe facial symmetry at rest and during movement (raise eyebrows, close eyes tightly, smile, puff cheeks). 1, 2
• Distinguish central from peripheral lesions: peripheral CN VII palsy affects the entire ipsilateral face including forehead; central (supranuclear) lesions spare forehead due to bilateral cortical innervation. 3
• Taste: anterior two-thirds of tongue (rarely tested clinically). 2

CN VIII (Vestibulocochlear)

• Hearing: whisper test or finger rub at arm's length from each ear. 2
• Weber and Rinne tests: if hearing loss detected. 2
• Vestibular function: assess for nystagmus, vertigo, balance disturbance. 2

CN IX, X (Glossopharyngeal, Vagus)

• Palate elevation: observe uvula position at rest and during phonation ("ah"); deviation suggests unilateral weakness. 1, 2
• Gag reflex: if clinically indicated (afferent CN IX, efferent CN X). 2
• Voice quality: assess for dysphonia, hoarseness, or nasal speech. 1
• Swallowing: observe for dysphagia, which occurs in 60-80% of advanced Parkinson's disease patients. 5

CN XI (Spinal Accessory)

• Shoulder shrug: test trapezius strength against resistance bilaterally. 1, 2
• Head turning: test sternocleidomastoid strength (turning head against resistance to opposite side). 2

CN XII (Hypoglossal)

• Tongue protrusion: observe for deviation (deviates toward side of lesion), atrophy, or fasciculations. 1, 2
• Tongue fasciculations: particularly important in suspected motor neuron disease. 1

Motor System Examination

Assess muscle bulk, tone, strength, and observe for involuntary movements. 1

Inspection

• Muscle bulk: look for atrophy or hypertrophy; asymmetry suggests lower motor neuron pathology. 1
• Fasciculations: spontaneous muscle twitching visible at rest, particularly in tongue and limbs, suggests motor neuron disease. 1
• Involuntary movements: tremor (rest vs. action), chorea, dystonia, myoclonus, tics. 1

Tone

• Test passive movement: assess resistance at major joints (wrist, elbow, knee, ankle). 1
• Rigidity: "lead-pipe" or "cogwheel" rigidity suggests parkinsonism; test for bradykinesia simultaneously. 1, 5
• Spasticity: velocity-dependent increased tone with "clasp-knife" phenomenon suggests upper motor neuron lesion. 1
• Hypotonia: decreased resistance suggests cerebellar, lower motor neuron, or acute upper motor neuron lesion. 1

Strength

• Grade systematically: use Medical Research Council (MRC) scale 0-5 for major muscle groups bilaterally. 1
• Proximal vs. distal: proximal weakness suggests myopathy; distal weakness suggests neuropathy. 1
• Functional assessment in children: observe antigravity movements in infants; assess ability to rise from floor (Gower sign indicates proximal weakness). 1
• Drift testing: pronator drift with arms extended and eyes closed suggests subtle upper motor neuron weakness. 1

Parkinsonian Features

• Bradykinesia: slowness of movement; test finger tapping, hand opening/closing, foot tapping with progressive decrement in amplitude and speed. 5
• Rest tremor: 4-6 Hz "pill-rolling" tremor present at rest, diminishes with action. 5
• Postural instability: pull test (stand behind patient and pull shoulders backward); inability to recover balance suggests advanced disease. 5

Sensory System Examination

Test multiple sensory modalities systematically, comparing side-to-side and distal-to-proximal. 1

Primary Sensory Modalities

• Light touch: cotton wisp or fingertip on face, trunk, and all four limbs. 1
• Pinprick: disposable pin testing pain sensation; map out any deficits. 1
• Temperature: if indicated (rarely performed routinely). 1
• Vibration: 128 Hz tuning fork on bony prominences (great toe, malleoli, fingers, wrists); loss suggests large fiber neuropathy. 1
• Proprioception: test position sense at distal joints (great toe, fingers) with eyes closed. 1

Cortical Sensory Function

• Two-point discrimination: tests parietal lobe function. 1
• Graphesthesia: identify numbers written on palm. 1
• Stereognosis: identify objects by touch alone. 1

Patterns of Sensory Loss

• Peripheral neuropathy: distal, symmetric "stocking-glove" distribution; most common in HCV-associated neuropathy is sensory or sensorimotor polyneuropathy. 1
• Radiculopathy: dermatomal distribution. 1
• Spinal cord lesion: sensory level on trunk. 1
• Hemisensory loss: suggests contralateral cortical or thalamic lesion. 1

Cerebellar Function Testing

Assess coordination, balance, and smooth execution of movements. 1

Coordination Tests

• Finger-to-nose: observe for intention tremor, dysmetria, or past-pointing. 1
• Heel-to-shin: slide heel down opposite shin; observe for ataxia. 1
• Rapid alternating movements: finger tapping, hand pronation-supination, foot tapping; dysdiadochokinesia suggests cerebellar dysfunction. 1

Gait and Station

• Observe gait: width of base, arm swing, turning, tandem walking. 1, 5
• Parkinsonian gait: shuffling steps, reduced arm swing, festination (accelerating forward), freezing episodes. 5
• Ataxic gait: wide-based, unsteady, irregular steps. 1
• Romberg test: stand with feet together, eyes open then closed; increased sway with eyes closed suggests proprioceptive or vestibular dysfunction, not cerebellar. 1

Speech Assessment

• Dysarthria: slurred, scanning, or staccato speech suggests cerebellar pathology. 1
• Hypophonia: soft, monotone speech is characteristic of Parkinson's disease. 5

Reflex Examination

Test deep tendon reflexes and pathological reflexes systematically. 1

Deep Tendon Reflexes

• Grade 0-4+: biceps (C5-6), triceps (C7-8), brachioradialis (C5-6), patellar (L3-4), Achilles (S1-2). 1
• Hyperreflexia with clonus: suggests upper motor neuron lesion. 1
• Hyporeflexia or areflexia: suggests lower motor neuron disorder, peripheral neuropathy, or acute upper motor neuron lesion (spinal shock). 1

Pathological Reflexes

• Babinski sign: upgoing great toe with fanning of other toes indicates upper motor neuron lesion (normal in infants <12-18 months). 1
• Primitive reflexes: grasp, snout, glabellar tap; persistence or reemergence suggests frontal lobe dysfunction or diffuse cerebral disease. 1

Infant-Specific Reflexes

• Moro reflex: should disappear by 4-6 months. 1
• Asymmetric tonic neck reflex: should disappear by 6 months. 1
• Persistence beyond expected age: suggests neuromotor dysfunction. 1

Meningeal Signs

Test for signs of meningeal irritation when infection or hemorrhage suspected. 1

• Neck stiffness: resistance to passive neck flexion. 1
• Kernig sign: pain/resistance when extending knee with hip flexed to 90 degrees. 1
• Brudzinski sign: involuntary hip/knee flexion when neck is flexed. 1

Vital Signs and General Physical Examination

Abnormal vital signs are key indicators of underlying medical conditions causing neurological symptoms. 1

• Blood pressure: measure bilaterally; orthostatic hypotension (drop >20 mmHg systolic or >10 mmHg diastolic) suggests autonomic dysfunction. 1
• Heart rate and rhythm: arrhythmias, particularly atrial fibrillation, increase stroke risk. 1
• Temperature: fever suggests infection (meningitis, encephalitis, abscess). 1
• Respiratory rate and pattern: abnormal patterns (Cheyne-Stokes, ataxic breathing) suggest brainstem dysfunction. 1
• Oxygen saturation: hypoxia can cause altered mental status and seizures. 1

Differential Diagnosis Framework

Acute/Subacute Presentations Requiring Urgent Evaluation

Rapidly progressive symptoms developing over hours to weeks demand immediate comprehensive workup. 1

Vascular Causes

• Stroke/TIA: sudden onset focal deficits; risk factors include hypertension, atrial fibrillation, diabetes. 1
• Intracerebral hemorrhage: headache, altered consciousness, focal deficits. 1
• Subarachnoid hemorrhage: sudden severe "thunderclap" headache, meningismus. 1
• Subdural/epidural hematoma: history of trauma (may be remote), progressive symptoms. 1
• CNS vasculitis: multifocal deficits, often with systemic symptoms; HCV-associated vasculitis presents with cryoglobulins. 1

Infectious/Inflammatory

• Meningitis: fever, headache, neck stiffness, altered mental status. 1
• Encephalitis: fever, altered mental status, seizures, focal deficits. 1
• Brain abscess: focal deficits, fever, headache; may have epidural or spinal involvement. 1
• HIV-related CNS disease: opportunistic infections, progressive multifocal leukoencephalopathy. 1

Metabolic/Toxic

• Hypoglycemia/hyperglycemia: altered mental status, seizures; check fingerstick glucose immediately. 1
• Hyponatremia: confusion, seizures, coma. 1
• Hypercalcemia/hypocalcemia: altered mental status, seizures. 1
• Uremia: encephalopathy, asterixis, myoclonus. 1
• Hepatic encephalopathy: altered mental status, asterixis, hyperammonemia. 1
• Thyroid storm/myxedema coma: altered mental status with thyroid dysfunction. 1

Toxicological

• Drug intoxication: alcohol, opioids, benzodiazepines, cocaine, amphetamines, synthetic cannabinoids. 1
• Drug withdrawal: alcohol, benzodiazepines (life-threatening). 1
• Carbon monoxide poisoning: headache, confusion, cherry-red skin (late finding). 1
• Organophosphate poisoning: cholinergic crisis with miosis, salivation, fasciculations. 1

Seizure-Related

• Seizures: convulsive or non-convulsive status epilepticus; post-ictal state. 1
• New-onset seizures: require workup for structural lesion, infection, metabolic derangement. 1

Chronic/Progressive Presentations

Symptoms developing over months to years suggest neurodegenerative, neoplastic, or chronic inflammatory processes. 1

Neurodegenerative Diseases

• Alzheimer's disease: progressive memory loss, executive dysfunction, preserved motor function until late stages. 1
• Behavioral variant frontotemporal dementia: personality changes, disinhibition, loss of empathy, executive dysfunction; often with preserved memory initially. 1
• Parkinson's disease: bradykinesia, rigidity, rest tremor, postural instability; may have cognitive impairment. 5
• Progressive supranuclear palsy: vertical gaze palsy, postural instability, parkinsonism. 1
• Corticobasal syndrome: asymmetric rigidity, apraxia, alien limb phenomenon. 1
• Multiple sclerosis: relapsing-remitting or progressive course; multiple CNS lesions separated in time and space. 1
• Huntington disease: chorea, psychiatric symptoms, family history. 1

Neoplastic

• Primary brain tumors: progressive focal deficits, headache, seizures. 1
• Metastatic disease: multiple lesions, known primary malignancy. 1
• Paraneoplastic syndromes: autoimmune CNS dysfunction associated with systemic malignancy. 1

Structural

• Hydrocephalus: gait disturbance, cognitive decline, urinary incontinence (normal pressure hydrocephalus triad). 1
• Congenital malformations: Chiari malformation, syringomyelia. 1

Vascular Cognitive Impairment

• Multi-infarct dementia: stepwise decline, focal deficits, vascular risk factors. 1
• Subcortical ischemic vascular disease: executive dysfunction, gait disturbance, white matter changes on imaging. 1

Psychiatric Mimics of Neurological Disease

Many medical conditions masquerade as primary psychiatric disorders; careful neurological examination distinguishes them. 1

Key Distinguishing Features

• Lack of insight: more prominent in frontotemporal dementia than primary psychiatric disorders. 1
• Motor signs: parkinsonism, dystonia, or motor neuron signs strongly suggest neurological disease over primary psychiatric disorder. 1
• Cognitive pattern: frontotemporal dementia shows executive dysfunction and behavioral changes with relatively preserved memory; psychiatric disorders typically have different patterns. 1
• Temporal course: neurodegenerative diseases show progressive decline; psychiatric disorders may fluctuate or respond to treatment. 1

Conditions to Consider

• Depression with pseudodementia: cognitive complaints exceed objective deficits; improves with antidepressant treatment. 1
• Psychosis: may be primary psychiatric or secondary to neurological disease (frontotemporal dementia, Lewy body dementia, autoimmune encephalitis). 1
• Anxiety disorders: may mimic or coexist with neurological disease. 1
• Conversion disorder: neurological symptoms without anatomical explanation; however, always rule out organic disease first. 1

Pediatric-Specific Considerations

Motor delays and developmental concerns require age-appropriate examination techniques. 1

Red Flags in Infants/Children

• Regression of skills: loss of previously acquired milestones always pathological. 1
• Asymmetry: unilateral weakness, reflex asymmetry, or preferential hand use before 18 months. 1
• Persistence of primitive reflexes: beyond expected age suggests neuromotor dysfunction. 1
• Microcephaly or macrocephaly: plot head circumference on growth curves; abnormal growth patterns require investigation. 1
• Gower sign: inability to rise from floor without using arms suggests proximal muscle weakness (muscular dystrophy). 1

Differential for Pediatric Motor Delays

• Upper motor neuron: cerebral palsy, spinal cord lesions. 1
• Lower motor neuron: spinal muscular atrophy, peripheral neuropathies. 1
• Neuromuscular junction: myasthenia gravis, congenital myasthenic syndromes. 1
• Muscle: congenital myopathies, muscular dystrophies. 1

Critical Pitfalls to Avoid

• Do not assume psychiatric diagnosis without thorough neurological examination: up to 50% of patients with CNS symptoms have underlying medical causes. 1, 6
• Do not rely solely on MMSE for cognitive screening: it misses early frontotemporal dementia and has poor sensitivity for executive dysfunction; use MoCA or ACE instead. 1
• Do not miss CN VI palsy as false localizing sign: isolated CN VI palsy can occur with increased intracranial pressure without direct nerve compression. 3
• Do not confuse central and peripheral facial palsy: peripheral CN VII palsy affects entire face including forehead; central lesions spare forehead. 3
• Do not overlook medication-induced symptoms: anticholinergics, antipsychotics, steroids, and many other drugs cause neurological symptoms. 1
• Do not perform routine urine drug screens without clinical indication: they rarely change management and should be reserved for cases where results will alter treatment. 1
• Do not miss delirium in psychiatric presentations: altered attention, fluctuating course, and acute onset suggest delirium requiring medical workup. 1
• Do not forget CNS involvement in systemic diseases: HCV, syphilis, HIV, sarcoidosis, lupus, and other systemic conditions affect the nervous system. 1