How to approach a case of Neurology: - What are the differential diagnoses that should be kept in mind when a patient has sensory deficit or sensory symptoms or motor symptoms or mixed ( picture of both motor and sensory ) and how to approach each case from history and physical examination? - What examination findings should be expected in neurological examination, for example, heart, mental function, cranial nerves, motor or sensory examination? - Especially how to approach a case of multiple sclerosis: what are its differential diagnoses and how to rule out each differential based on history, physical examination, and investigations readily available?
Reading File
Finding Sources
Finding Sources
Finding Sources
How to approach a case of Neurology: - What are the differential diagnoses that should be kept in mind when a patient has sensory deficit or sensory symptoms or motor symptoms or mixed ( picture of both motor and sensory ) and how to approach each case from history and physical examination? - What examination findings should be expected in neurological examination, for example, higher mental function, cranial nerves, motor or sensory examination? - Especially how to approach a case of multiple sclerosis: what are its differential diagnoses and how to rule out each differential based on history, physical examination, and investigations readily available
Reading File
Finding Sources
Finding Sources
Finding Sources
Finding Sources
Finding Sources
Finding Sources
Finding Sources
Reading File
Reading File
Reading File
Reading File
Finding Sources
Reading File
Reading File
Reading File
Reading File
Reading File
Reading File
Reading File
Finding Sources
Reading File
Finding Sources
Here is the full, structured clinical guide synthesized from Adams and Victor's Principles of Neurology and Bradley and Daroff's Neurology in Clinical Practice.
Approaching a Neurology Case: A Systematic Clinical Guide
PART 1: THE FUNDAMENTAL PRINCIPLE - LOCALIZATION FIRST
The single most important step in neurology is anatomical localization - answering "where is the lesion?" before asking "what is it?" The pattern of deficits tells you where the lesion is, and the location dramatically narrows the differential diagnosis.
The neuraxis levels to localize to are:
- Cerebral cortex / subcortical white matter
- Basal ganglia / thalamus
- Brainstem (midbrain, pons, medulla)
- Cerebellum
- Spinal cord (cervical, thoracic, lumbar, conus, cauda equina)
- Nerve roots (radiculopathy)
- Peripheral nerve (mononeuropathy, polyneuropathy, plexopathy)
- Neuromuscular junction
- Muscle (myopathy)
PART 2: DIFFERENTIAL DIAGNOSES BY SYMPTOM PATTERN
A. Pure Sensory Symptoms / Sensory Deficit
The type of sensory loss tells you which fiber types and anatomical tracts are involved:
| Symptom | Fiber Type | Location |
|---|---|---|
| Tingling, pins-and-needles ("Novocaine") | Large myelinated fibers | Peripheral nerve or posterior columns |
| Burning pain, hyperpathia | Small-fiber (A-delta, C) | Small-fiber neuropathy, spinothalamic tract |
| Band-like / girdle sensation on trunk | Large-fiber | Posterior columns or peripheral nerve |
| Lancinating pains radiating to back/neck | Root or sensory ganglion disease | Nerve root, dorsal root ganglion |
| Loss of pain/temperature WITH preserved touch | Spinothalamic tract only | Syringomyelia, anterior cord syndrome, Brown-Sequard |
| Loss of vibration/position WITH preserved pain/temp | Posterior columns only | Subacute combined degeneration (B12 deficiency), MS posterior column plaque, tabes dorsalis |
| All modalities lost distally and symmetrically | Multiple peripheral nerves | Polyneuropathy (diabetic, alcoholic, nutritional) |
Key differentials for sensory symptoms:
| Diagnosis | Key Features |
|---|---|
| Polyneuropathy | Symmetric distal ("stocking-glove"), areflexia/hyporeflexia; weakness if present is symmetric |
| Radiculopathy | Dermatomal distribution, may radiate, worsens with Valsalva, straight-leg raise positive |
| Posterior column disease (B12 deficiency, tabes, MS) | Loss of vibration/position sense, sensory ataxia, Romberg positive |
| Syringomyelia | Dissociated loss - pain/temperature lost, touch preserved; "cape distribution" over neck/arms |
| Brown-Séquard (cord hemisection) | Ipsilateral proprioception loss + contralateral pain/temperature loss, ipsilateral UMN signs |
| Complete transverse myelopathy | All modalities below a level, UMN signs, sphincter dysfunction |
| Thalamic lesion | Contralateral hemisensory loss of all modalities; may have "thalamic pain" (burning, spontaneous) |
| Cortical sensory loss | Discriminative senses affected (stereognosis, graphesthesia, two-point discrimination) with intact primary sensation |
| Ganglionopathy | All modalities affected, proximal body parts involved, sensory ataxia prominent |
B. Pure Motor Symptoms
The key distinction is UMN (upper motor neuron) vs LMN (lower motor neuron):
| Feature | UMN | LMN |
|---|---|---|
| Tone | Spastic (increased) | Flaccid (decreased) |
| Reflexes | Hyperreflexia | Hyporeflexia / areflexia |
| Plantar response | Extensor (Babinski +) | Flexor or absent |
| Fasciculations | Absent | Present |
| Atrophy | Late, disuse | Early, prominent |
| Weakness distribution | Pyramidal pattern (extensors > flexors in arms, flexors > extensors in legs) | Focal or generalized |
Key differentials for motor symptoms:
| Diagnosis | Location | Clues |
|---|---|---|
| Stroke / TIA | Cerebral cortex / internal capsule | Sudden onset, hemiplegia, facial involvement, cortical signs (aphasia, neglect) |
| ALS | UMN + LMN simultaneously | Wasting + hyperreflexia + fasciculations in same patient, no sensory loss |
| Cervical myelopathy | Cervical cord | UMN in legs, LMN at the level, neck pain, hand clumsiness |
| GBS (Guillain-Barré) | Peripheral nerves | Ascending flaccid paralysis, areflexia, post-infectious, CSF: albuminocytologic dissociation |
| Myasthenia Gravis | NMJ | Fatigable weakness, ptosis, diplopia, worsens at end of day, normal reflexes and sensation |
| Myopathy | Muscle | Proximal > distal, symmetrical, preserved reflexes until late, no sensory loss |
| MS | CNS white matter | Relapsing-remitting, young adult, UMN signs, MRI white matter lesions |
| Spinal cord compression | Spinal cord | UMN below level + LMN at level, sensory level, bladder/bowel dysfunction |
C. Mixed Motor + Sensory (Most Common Combination)
When both motor and sensory features coexist, the combined pattern localizes the lesion:
| Pattern | Location |
|---|---|
| Ipsilateral UMN + ipsilateral proprioception loss + contralateral pain/temperature loss | Spinal cord hemisection (Brown-Séquard) |
| UMN signs in legs + sensory level + bladder dysfunction | Spinal cord (myelopathy) |
| Dermatomal sensory loss + segmental muscle weakness + reflex loss at that level | Nerve root (radiculopathy) |
| Cranial nerve palsy + contralateral long-tract signs | Brainstem lesion (crossed syndrome) |
| Ipsilateral face + contralateral body, hemiplegia + hemisensory | Internal capsule / corona radiata |
| Symmetric distal sensory + distal weakness + areflexia | Peripheral neuropathy |
| Distal weakness + sensory loss in ulnar/median/radial distribution | Mononeuropathy / entrapment |
Key differentials for mixed motor+sensory:
| Diagnosis | History clue | Exam clue |
|---|---|---|
| MS | Relapsing, young female, optic neuritis, heat sensitivity (Uhthoff) | INO, Lhermitte sign, spastic paraparesis, relative afferent pupillary defect |
| Cervical spondylotic myelopathy | Older patient, neck pain, insidious | UMN in legs, LMN/sensory at cervical level, wasted hand muscles |
| B12 deficiency (SCD) | Vegetarian, anemia, psychiatric symptoms | Posterior column + corticospinal tract, macrocytic anemia, glossitis |
| HTLV-1 myelopathy | Endemic area, sexual transmission | Spastic paraparesis, hyperreflexia, sphincter dysfunction |
| Syringomyelia | Young adult, Chiari, scoliosis | Cape distribution dissociated sensory loss, wasted arms, UMN legs |
| Spinal cord infarction | Sudden onset, vascular risk factors | Anterior cord syndrome (motor + pain/temp loss, spared vibration/position) |
| Vasculitis / SLE | Systemic symptoms, multisystem | CNS + PNS both affected, rash, serology positive |
PART 3: THE NEUROLOGICAL EXAMINATION - WHAT TO LOOK FOR
1. Higher Mental Function (Cognitive Screen)
This begins during history-taking. Assess:
- Orientation - person, place, time (tests memory encoding)
- Insight into illness - is the patient aware they are unwell?
- Language - fluency, comprehension, naming, repetition (during natural conversation)
- Non-fluent aphasia with good comprehension = Broca (frontal, dominant)
- Fluent aphasia with poor comprehension = Wernicke (temporal, dominant)
- Anomia + reading/writing problems = angular gyrus
- Memory - short-term: 3-item recall at 5 minutes; long-term: remote historical events
- Attention / concentration - serial 7s, spelling "WORLD" backwards
- Praxis - ability to carry out learned motor tasks on command
- Visuospatial - clock drawing, copying figures
2. Cranial Nerve Examination
| CN | What to test | Abnormal finding |
|---|---|---|
| I (Olfactory) | Smell each nostril separately | Anosmia - frontal lobe tumor, head trauma |
| II (Optic) | Visual acuity (Snellen), visual fields (confrontation), fundoscopy, pupil direct/indirect reaction | RAPD (Marcus Gunn pupil) = ipsilateral optic nerve disease; papilledema = raised ICP; optic atrophy |
| III, IV, VI (Oculomotor) | Extraocular movements in 9 positions, pupil size/reactivity, lid position | Ptosis + dilated pupil = CN III palsy; INO = MLF lesion (MS); 6th nerve palsy = raised ICP or MS or brainstem; nystagmus = cerebellar or brainstem |
| V (Trigeminal) | Facial sensation (3 divisions: V1 forehead, V2 cheek, V3 chin), corneal reflex | Loss of corneal = early V1 lesion; jaw deviation on opening = pterygoid weakness |
| VII (Facial) | Raise eyebrows, close eyes tightly, show teeth, puff cheeks | UMN: forehead spared (bilateral cortical input); LMN (Bell's): entire face including forehead |
| VIII (Vestibulo-cochlear) | Hearing (whispered voice, Rinne/Weber), nystagmus | Sensorineural vs conductive hearing loss; Rinne and Weber distinguish |
| IX, X (Glossopharyngeal, Vagus) | Gag reflex, palate elevation, voice quality | Hoarseness, dysphagia, nasal regurgitation; palate deviates away from lesion |
| XI (Accessory) | Shrug shoulders (trapezius), turn head against resistance (SCM) | Weakness indicates posterior fossa or neck lesion |
| XII (Hypoglossal) | Tongue protrusion, lateral movements, atrophy/fasciculations | Tongue deviates toward side of lesion; fasciculations = LMN (ALS) |
Important cranial nerve syndromes:
- Relative Afferent Pupillary Defect (RAPD/Marcus Gunn): Swing flashlight test - affected eye paradoxically dilates when light moves to it. Indicates optic nerve disease ipsilaterally (classic in MS optic neuritis)
- Internuclear Ophthalmoplegia (INO): Impaired adduction one eye + abducting nystagmus of other eye on lateral gaze. Due to MLF lesion. Bilateral INO is highly characteristic of MS.
- Horner syndrome (ptosis, miosis, anhidrosis): central (hypothalamus-spinal cord), preganglionic (lung apex, neck), or postganglionic (cavernous sinus, orbit)
3. Motor Examination
- Inspection: Wasting, fasciculations, abnormal posture
- Tone: Spasticity (clasp-knife), rigidity (lead-pipe or cogwheel), hypotonia (cerebellar, LMN)
- Power: MRC grading 0-5; test in pyramidal distribution (deltoid, wrist extensors, finger extensors, hip flexors, knee flexors, ankle dorsiflexors)
- Reflexes:
- Deep tendon reflexes: biceps (C5,6), brachioradialis (C6), triceps (C7), patellar (L3,4), Achilles (S1)
- Grade 0 (absent) to 4+ (clonus); absent = LMN/peripheral; hyperreflexia = UMN
- Plantar response: Babinski sign (extensor plantar) = UMN lesion
- Clonus: Sustained rhythmic contractions at ankle or patella = UMN
- Hoffman sign: Flick the middle finger nail - flexion of thumb and index = UMN in upper limb
Pronator drift: Outstretched arms, eyes closed - UMN weakness causes supination and downward drift on the affected side
4. Coordination and Cerebellar Signs
- Finger-nose test: Dysmetria (past-pointing) and intention tremor = cerebellar
- Heel-shin test: Ipsilateral cerebellar disease causes imprecision
- Dysdiadochokinesis: Impaired rapid alternating movements
- Gait: Ataxic broad-based gait = cerebellar; scissors gait = spastic; steppage = foot drop; festinating = Parkinson's
5. Sensory Examination (tested last, requires a cooperative patient)
- Light touch: Cotton wool; loss in a dermatomal, peripheral nerve, or "level" pattern
- Pain (pinprick): Disposable pin; dissociated loss from touch = spinothalamic involvement
- Vibration (128 Hz tuning fork): Toes/ankles/knees, fingers/wrists; lost early in posterior column and large-fiber neuropathy
- Joint position sense (proprioception): Distal phalanx - small movements; loss = posterior column or large-fiber neuropathy; test with Romberg (positive = falls with eyes closed = sensory ataxia)
- Temperature: Hot/cold test tubes; lost with spinothalamic (pain) fibers
- Cortical sensation: Stereognosis (identify object by touch), graphesthesia (number traced on palm), two-point discrimination
The Romberg test: Stand with feet together, arms out. Eyes open = cerebellar ataxia is evident. Eyes closed, unsteady = positive Romberg = posterior column/sensory ataxia.
6. Gait Assessment
Always observe gait as part of the neurological exam. The pattern is often the single most informative observation:
| Gait pattern | Implies |
|---|---|
| Spastic-scissors gait | Bilateral UMN (spinal cord or bilateral cerebral) |
| Hemiplegic (circumduction) | Contralateral UMN hemisphere lesion |
| Steppage (foot slap) | Foot drop - peroneal nerve, L4/5 root, anterior horn |
| Cerebellar ataxic (broad-based, staggering) | Cerebellar or vestibular |
| Sensory ataxic (stamping, eyes help) | Posterior columns - worse in dark/eyes closed |
| Parkinsonian (shuffling, festinating) | Basal ganglia |
| Antalgic (pain-avoiding) | Musculoskeletal |
PART 4: APPROACH TO MULTIPLE SCLEROSIS (MS)
What is MS?
MS is a chronic autoimmune inflammatory demyelinating disease of the CNS white matter. The hallmark is dissemination in space (DIS) and dissemination in time (DIT) - lesions in multiple CNS locations at multiple time points.
- Peak age of onset: 25-30 years (range 15-50)
- Female:male = 2-3:1 in relapsing-remitting MS; 1:1 in primary progressive MS
- More common at higher latitudes
Clinical Features Suggestive of MS
(From Bradley and Daroff's Neurology in Clinical Practice)
- Onset between ages 15 and 50
- Involvement of multiple CNS areas over time (DIS + DIT)
- Optic neuritis (unilateral painful visual loss + RAPD)
- Lhermitte sign: Electric shock sensation down the spine on neck flexion (posterior column involvement)
- Internuclear ophthalmoplegia (INO): Bilateral INO is pathognomonic of MS in a young adult
- Fatigue - often disproportionate to disability
- Uhthoff phenomenon: Worsening with heat/fever/exercise (characteristic)
- Transient paroxysmal symptoms: Paroxysmal dysarthria, tonic spasms, sensory episodes lasting seconds-minutes
Common Clinical Presentations (Disease-Onset Scenarios)
| Presentation | What to think |
|---|---|
| Optic neuritis (painful monocular visual loss) | 50% develop MS over 15 years (higher risk if MRI lesions present) |
| Transverse myelitis (paraparesis + sensory level + bladder) | Partial myelitis more characteristic of MS than complete transverse myelitis |
| INO in young person | MS until proven otherwise |
| Brainstem syndrome (vertigo, diplopia, dysarthria, facial numbness) | CIS (clinically isolated syndrome) - may be first attack of MS |
| Relapsing-remitting course | Classic - attacks over days/weeks, recovery over weeks/months |
| Progressive paraparesis after 40 | Consider PPMS, HTLV-1, cervical myelopathy, hereditary spastic paraparesis |
McDonald 2017 Diagnostic Criteria (Simplified)
Two attacks + two objective clinical lesions = MS (no further testing needed)
If incomplete, demonstrate DIS and DIT by MRI or CSF:
- DIS by MRI: Lesions in 2+ of 4 areas: periventricular, cortical/juxtacortical, infratentorial, spinal cord
- DIT by MRI: New T2 or enhancing lesion on follow-up MRI OR simultaneous presence of enhancing and non-enhancing lesions
- CSF oligoclonal bands (OCBs) substitute for DIT
Investigations in MS
| Investigation | Finding in MS | Significance |
|---|---|---|
| MRI brain + spine (with gadolinium) | T2/FLAIR periventricular, juxtacortical, infratentorial white matter lesions; open-ring or homogeneous enhancement of active plaques; T1 "black holes" = permanent damage; spinal cord lesions <2 vertebral segments, asymmetric | Most important test; gadolinium enhancement = active inflammation |
| CSF analysis | Clear, normal pressure; lymphocytic pleocytosis <50 cells (>50 cells raises suspicion of alternative dx); OCBs in IgG region (absent in serum) = 90% sensitive for MS; elevated IgG index; myelin basic protein (MBP) in acute attacks | OCBs most important CSF marker |
| Evoked potentials | Delayed VEP (visual evoked potential) = subclinical optic nerve involvement even without clinical ON | Useful to demonstrate DIS objectively when clinical findings insufficient |
| Blood tests | Serum AQP4-IgG (aquaporin-4 antibody) and MOG-IgG to exclude NMO/MOGAD; serum B12, folate; ANA/anti-dsDNA for SLE; ACE for sarcoidosis; VDRL for neurosyphilis; HIV; HTLV-1 serology | Rule out mimics |
DIFFERENTIAL DIAGNOSES OF MS and How to Rule Each Out
(From Bradley and Daroff's Neurology BOX 80.2)
1. Neuromyelitis Optica Spectrum Disorder (NMOSD)
- How it mimics MS: Severe optic neuritis (often bilateral), transverse myelitis, brainstem lesions
- How to differentiate:
- Myelitis is LONGITUDINALLY EXTENSIVE (>3 vertebral segments) vs MS (<2 segments)
- Bilateral simultaneous optic neuritis (rare in MS)
- Area postrema lesions (intractable hiccups, nausea/vomiting)
- AQP4-IgG (anti-aquaporin-4) positive in ~75% - highly specific; if positive, rules out MS
- OCBs usually absent in NMOSD
- MS treatments (interferon-beta, natalizumab) can worsen NMOSD
2. MOG Antibody-Associated Disease (MOGAD)
- How it mimics MS: Optic neuritis, myelitis, brainstem/cortical syndromes
- How to differentiate:
- MOG-IgG serum antibody positive - rules in MOGAD
- Optic nerve involvement often bilateral with perineural enhancement
- Myelitis often longitudinally extensive
- ADEM-like presentation common in children
- OCBs usually absent
3. Acute Disseminated Encephalomyelitis (ADEM)
- How it mimics MS: White matter lesions, multifocal neurological deficits
- How to differentiate:
- Usually monophasic (one attack, no relapses)
- Preceded by infection or vaccination (2-4 weeks)
- Prominent encephalopathy (confusion, altered consciousness) - very uncommon in MS
- More common in children
- Large, "tumefactive" lesions, cortical gray matter involvement
- History and monophasic course are key - watch for relapse (if relapse occurs, reconsider MS/MOGAD)
4. Systemic Lupus Erythematosus (SLE)
- How it mimics MS: CNS white matter lesions, optic neuritis, myelitis, relapsing course
- How to differentiate:
- Systemic features: malar rash, photosensitivity, serositis, arthritis, renal disease, oral ulcers
- Serology: ANA, anti-dsDNA, anti-Sm antibodies; low complement C3/C4; APL antibodies
- Libman-Sacks endocarditis on echo; proteinuria/hematuria
- CNS vasculitis with stroke-like lesions in gray matter distribution (not typical MS white matter periventricular pattern)
5. Neurosarcoidosis
- How it mimics MS: Cranial nerve palsies, optic nerve lesions, white matter lesions, myelopathy
- How to differentiate:
- Bilateral facial palsy (rare in MS)
- Leptomeningeal enhancement on MRI (not seen in MS)
- Pulmonary hilar adenopathy on CXR/CT
- Serum ACE elevated (50-80% sensitive)
- Elevated 24-hour urine calcium; hypercalcemia
- Tissue biopsy (lymph node, skin, or transbronchial) showing non-caseating granulomas
6. CNS Vasculitis / Granulomatous Angiitis
- How it mimics MS: White matter lesions, multifocal neurological deficits, relapsing course
- How to differentiate:
- Headache often prominent
- Stroke/TIA-like events in young adult
- Gray matter lesions + white matter on MRI; may show restricted diffusion
- CSF: pleocytosis + elevated protein (more inflammatory than MS)
- Cerebral angiography: beading pattern; brain biopsy definitive
7. Sjögren Syndrome
- How it mimics MS: White matter lesions, optic neuropathy, myelopathy, peripheral neuropathy
- How to differentiate:
- Sicca symptoms: dry eyes (keratoconjunctivitis sicca), dry mouth (xerostomia)
- Serology: anti-Ro (SSA) and anti-La (SSB) antibodies, positive ANA
- Schirmer test (tear production), minor salivary gland biopsy (lymphocytic infiltration)
- Peripheral neuropathy (sensory ganglionopathy) - uncommon in MS
8. Behçet Disease
- How it mimics MS: CNS white matter lesions, brainstem lesions, optic neuropathy
- How to differentiate:
- Oral ulcers (recurrent, painless/painful)
- Genital ulcers
- Uveitis, skin lesions (erythema nodosum, pseudofolliculitis)
- Pathergy test positive (skin prick reaction)
- Brainstem lesions tend to be large and confluent
9. Vitamin B12 Deficiency (Subacute Combined Degeneration)
- How it mimics MS: Posterior column signs (vibration/position sense loss), pyramidal signs
- How to differentiate:
- Macrocytic anemia on CBC; elevated MCV
- Low serum B12; elevated methylmalonic acid and homocysteine (more sensitive)
- Peripheral neuropathy (in addition to cord signs) - unusual in MS
- Glossitis, angular stomatitis; dietary history (vegan, malabsorption, pernicious anemia)
- No relapses and remissions; MRI shows T2 signal in posterior and lateral columns of cord
10. Lyme Neuroborreliosis
- How it mimics MS: White matter lesions, multifocal neurological signs, cranial nerve palsies
- How to differentiate:
- Tick exposure history, endemic area (northeastern US, northern Europe)
- Erythema migrans rash (pathognomonic)
- Bilateral CN VII palsy highly suggestive
- Serology: ELISA + Western blot for Borrelia burgdorferi
- CSF: lymphocytic pleocytosis, elevated protein (more marked than MS)
- Responds to antibiotics (doxycycline/ceftriaxone)
11. HTLV-1 Myelopathy (Tropical Spastic Paraparesis)
- How it mimics MS: Progressive spastic paraparesis, cord lesions
- How to differentiate:
- Endemic area: Caribbean, Japan, Africa; risk factors include sexual transmission, IV drug use, breastfeeding
- Primarily progressive (no relapsing-remitting course)
- HTLV-1 serology positive in blood and CSF
- No optic neuritis or cerebellar features
12. Progressive Multifocal Leukoencephalopathy (PML)
- How it mimics MS: White matter lesions, multifocal deficits
- How to differentiate:
- Immunocompromised state: HIV/AIDS, natalizumab therapy, other immunosuppressants
- Subacute progressive decline without relapses/remissions
- JC virus DNA in CSF (PCR); large confluent subcortical lesions without enhancement
- No gadolinium enhancement in most cases (unlike active MS)
13. HIV-Associated Myelopathy / Encephalopathy
- How it mimics MS: White matter lesions, progressive myelopathy
- How to differentiate:
- Risk factors for HIV; rash, lymphadenopathy, weight loss
- HIV serology (ELISA + Western blot)
- Peripheral neuropathy common; CD4 count
- Vacuolar myelopathy: posterior and lateral columns, often in advanced AIDS
14. Adrenomyeloleukodystrophy (ALD) / Metachromatic Leukodystrophy
- How it mimics MS: White matter lesions, progressive spastic paraparesis in young adults
- How to differentiate:
- Family history (X-linked in ALD), young adult males
- Adrenal insufficiency (hyperpigmentation, hypotension, electrolyte abnormalities) in ALD
- MRI: symmetric posterior periventricular lesions ("butterfly pattern") in ALD - distinct from MS asymmetric periventricular lesions
- Very long chain fatty acids (VLCFA) elevated in ALD
- Arylsulfatase A deficiency in MLD
15. Spinocerebellar Ataxia / Hereditary Spastic Paraparesis
- How it mimics MS: Ataxia, spastic paraparesis, white matter changes
- How to differentiate:
- Family history (autosomal dominant/recessive)
- Progressive from onset, no relapses
- Genetic testing available for most types
- Slowly progressive course over decades
16. Cervical Spondylotic Myelopathy
- How it mimics MS: Spastic paraparesis, sensory loss, progressive course
- How to differentiate:
- Older patient (>50 years), neck pain/stiffness, radiculopathy
- MRI spine: cord compression at disc/osteophyte level, signal change in cord
- No optic neuritis, no brainstem signs, no periventricular brain lesions
- History of trauma or mechanical neck symptoms
17. Arnold-Chiari Malformation
- How it mimics MS: Cerebellar ataxia, nystagmus, brainstem signs, syringomyelia
- How to differentiate:
- MRI: tonsillar herniation below foramen magnum >5mm
- May have associated syringomyelia
- No periventricular white matter lesions of MS
- No relapses
A Practical Investigation Ladder for a Suspected MS Case
Step 1 - Blood tests to exclude mimics:
- CBC (macrocytosis for B12 deficiency)
- Serum B12, folate
- ANA, anti-dsDNA, anti-Ro, anti-La (SLE, Sjögren)
- ACE (sarcoidosis)
- VDRL + TPHA (neurosyphilis)
- HIV serology
- HTLV-1 (endemic areas)
- Serum AQP4-IgG and MOG-IgG (NMOSD, MOGAD)
- Thyroid function (thyroid eye disease can mimic optic nerve issues)
- Very long chain fatty acids if young male with progressive disease
Step 2 - Imaging:
- MRI brain + spinal cord with gadolinium - the single most important investigation
- T2/FLAIR periventricular "Dawson fingers" (lesions perpendicular to ventricles), juxtacortical, infratentorial, cord lesions
- T1 post-contrast: active enhancing plaques (open ring > ring enhancement in MS)
- T1 black holes = chronic axonal loss
Step 3 - CSF (when diagnosis uncertain):
- Cell count, protein, glucose
- CSF-specific oligoclonal bands (IgG) - absent in serum
- IgG index (>0.7 supports intrathecal synthesis)
- Myelin basic protein
- JC virus PCR (if PML suspected), Borrelia antibodies (if Lyme suspected)
Step 4 - Evoked potentials:
- Visual evoked potentials (VEPs): delayed P100 latency = subclinical optic nerve demyelination
- Somatosensory and brainstem auditory evoked potentials: demonstrate subclinical DIS
Red Flags Against MS (Think Again)
These features should prompt reconsideration of the MS diagnosis:
- Age of onset <10 or >60 years
- Progressive from very onset in young patient
- Bilateral simultaneous optic neuritis
- Longitudinally extensive myelitis (>3 segments)
- Prominent encephalopathy or seizures at onset
- Systemic features (rash, arthritis, serositis, uveitis, dry eyes/mouth)
- CSF pleocytosis >50 cells or low glucose
- Peripheral neuropathy (not explained by MS alone)
- Male + progressive + family history (consider hereditary)
- Normal MRI brain after 2 clinical attacks
- No response to steroids for acute attack
Sources: Adams and Victor's Principles of Neurology, 12th Edition; Bradley and Daroff's Neurology in Clinical Practice, 8th Edition
This is a shared conversation. Sign in to Orris to start your own chat.