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DEMYELINATING DISEASES
Pathologic Criteria of a Demyelinating Disease: CNS: Oligodendrocytes (1:many) Physiologic Effects of Demyelination:
● Destruction of myelin sheaths of nerve fibers ● Affects saltatory conduction of nerve impulses
● Infiltration of inflammatory cells (perivenous distribution) ● Temporary induction, by heat or exercise (↑ 0.5°C→block electrical transmission)
● Lesions that are primarily in the white matter PNS: Schwann cells (1:1)
● Sensitivity of demyelinated and remyelinated regions to subtle metabolic and
(white-axons; gray-soma/neuron) environmental changes (smoking, fatigue, hyperventilation)

MULTIPLE SCLEROSIS
EPIDEMIOLOGY CLINICAL MANIFESTATIONS PATHOLOGIC FINDINGS DIAGNOSTIC CRITERIA TREATMENT
- Most common inflammatory EARLY SIGNS & SYMPTOMS: Pathologic findings: Criteria:
demyelinating disease - Weakness / numbness of limbs ● Pink-gray color (loss of myelin) ● ≥2 attacks, ≥2 lesions General:
- 2-3x higher in women - Tingling of extremities ● Lesions distributed in brainstem, ● Fatigue – amantadine
- Unimodal age-specific onset - Tight, bandlike sensations around spinal cord, and cerebellar ● ≥2 attacks, 1 lesion ● Urinary retention – bethanecol Cl
(~30 yo) the trunk peduncles + DIS: ≥2 T2 lesions in JIPS* ● Constipation – enemas
- Genetic: highest risk in siblings - Incoordination ● Degeneration of oligodendroglia ● Pain - carbamazepine
with MS - Hyperactive tendon reflexes ● 1 attack, ≥2 lesions ● Postural tremor - isoniazid
- Environmental: trauma, - Lhermitte sign - flex neck→ tingling MRI + DIT: enhancing & nonenhancing ● Severe disabling tremor –
infection (Chlamydia, HPV-6) sensation sa spine - T2 hyperintense lesions lesions or new lesion unresponsive to meds, do surgery
- most helpful ancillary, reveals (ventrolateral thalamotomy)
Worse prognosis: ESTABLISHED DISEASE: asymptomatic (cerebral) and ● 1 attack, 1 lesion (CIS)
- Male - Cognitive impairment (~50%): symptomatic (spinal cord, + DIS or DIT criteria Multiple sclerosis:
- Late age of onset (>40 yo) ↓attention, ↓memory, preserved brainstem) ● Immunomodulatory therapy
- Motor symptoms from onset language skills - Dawson fingers ● Progressive deficits of MS ● Glucocorticoids (IV methylprednisone-
- Progressive type from onset - Depression + 1 yr progression or CSF taper slowly!)
- Poor recovery from first attack - Bladder dysfunction CSF analysis: oligoclonal bands
- Paroxysmal attacks of neurologic - Oligoclonal bands – most widely Optic neuritis:
Favorable prognosis: deficit: dysarthria and ataxia (well- used (in CSF) *Typical locations of MS Plaques: ● Methylprednisone: IV→oral
- Female recognized feature of MS) - Total protein - Juxtacortical ● Glatiramer – NO antibodies
- Onset before age 40 - Severe fatigue - Radioimmunoassay: - Infratentorial (brainstem & ● Other immunosuppressive drugs
- Visual/somatosensory cerebellum)
presentation - Periventricular

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Syndromes - Spinal cord

Variants of MS: ● Optic neuritis
● Marburg variant – large, acute ● Transverse myelitis Histologic Subgroups Pattern:
plaques, NO oligoclonal bands; ● Cerebellar ataxia ● 1 – Inflammatory lesions
rare, life-threatening ● Brainstem syndromes (vertigo, (T cells & macrophages)
facial numbness, diplopia)
● Concentric sclerosis of Balo – ● 2 – Autoantibody lesions
alternating bands of myelin Types of MS (Clinical course): (w/ IgG, complement)
destruction and preservation ● Relapsing-remitting – most
common; with full recovery, plateaus ● 3 – Apoptosis of
● Schilder disease – cerebrum ● Secondary-progressive – initial oligodendrocytes (NO IgG,
site of diffuse and massive RRMS → progression complement)
demyelination ● Primary-progressive – disease
progression from onset, minor ● 4 – Only oligodendrocyte
● MS + Peripheral neuropathy – recovery dystrophy (NO remyelination)
demyelinating lesions in central ● Progressive-relapsing – disease
white matter and peripheral progression from onset, +/- full
nerves recovery

DIAGNOSTIC CRITERIA FOR MULTIPLE SCLEROSIS

CLINICAL FEATURES ADDITIONAL DATA NEEDED
≥2 clinical attacks, with objective evidence of 2 lesions None. DIS and DIT have been met.
≥2 clinical attacks, with objective evidence of 1 lesion One of the following (for DIS):
- ≥2 T2 hyperintense lesions in JIPS
- Additional clinical attack at different CNS site
1 attack, with objective evidence of ≥2 lesions One of the following (for DIT):
- Simultaneous enhancing and nonenhancing lesions
- New T2 hyperintense lesion vs prior scan
- Additional clinical attack
1 attack, with objective evidence of 1 lesion *CIS DIS and DIT criteria as above.
Progressive, nonrelapsing deficits suggestive of MS 1 year disease progression, and either:
- DIS criteria as above
- Oligoclonal bands in CSF

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OTHER DEMYELINATING DISEASES

DISEASE, DEFINITION EPIDEMIOLOGY CLINICAL MANIFESTATIONS LABS (PATHOLOGIC FINDINGS) TREATMENT
Neuromyelitis Optica Features: MRI – hyperintense, longitudinally ● High-dose corticosteroids
- aka “Asian optic-spinal MS” ● Onset of blindness extensive cervicothoracic lesion ● IV Immunoglobulin
Binding of NMO-IgG to AQP4 → ● Severe transverse / ascending ● Immunosuppressive drugs
antibodies and complement myelitis - Azathioprine
system → astrocytic injury (optic - Cyclophosphamide
nerves & spinal cord) ● Aggressive, monophasic - AQP4 antibody blocker
*bigla nalang nabulag or naparalyze
waist down

Characterized by involvement of optic

nerves and spinal cord

Acute Disseminated - Can be post-infectious, post- Latency: 3-4 weeks Pathology: ● IV Methylprednisone for 3-5
Encephalomyelitis (ADEM) exanthem, post-vaccinal - Numerous foci of demyelination days
encephalomyelitis ● Ataxia, confusion, somnolence, scattered throughout brain and spinal ● Plasma exchange
Immune-mediated complication convulsions with headache cord ● IV immunoglobulin
of infection (rather than direct - More common in children ● Fever, stiff neck - Regions of white matter invaded by
infection of CNS) ● Stupor, coma, decerebrate rigidity monocytes and microglia
*histologically indistinguishable from
POST-EXANTHEM acute MS
● Syndrome begins 2-4 days after
appearance of the rash CSF: ↑lymphocytes, ↑protein
MRI: several bilateral confluent white
POST-VACCINAL matter lesions
● Rare complication of rabies
vaccine; 30-50% mortality

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Acute Necrotizing Hemorrhagic - aka “Weston Hurst” Pathology: ● High-dose corticosteroids

Encephalomyelitis ● Headache, fever, stiff neck - White matter is destroyed almost to ● Plasma exchange
- Affects mainly young adults and the point of liquefaction ● IV immunoglobulin
Fulminant form of demyelinating children - Tissue is pink / yellow-gray, with
disease / ADEM - Usually preceded by respiratory multiple petechial hemorrhages
infection due to Mycoplasma - Widespread necrosis of blood vessels
pneumoniae & brain

- those who recovered develop CSF: ↑pressure

typical MS
CT & MRI:
- Bilateral but asymmetrical large,
confluent, edematous lesions in the
cerebral white matter
- Punctuate hemorrhages in gray and
white matter

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DEGENERATIVE DISEASES
General Pathologic Features of Degeneration
● Neuronal degeneration (cell death → glial scar) Clinical Classification of Neurodegenerative Diseases:
● Selective involvement of anatomically and physically related neurons 1 – Syndrome of progressive dementia, other neuro signs absent or inconspicuous
● Protein aggregation → continuous spread via synaptic connections 2 – Syndrome of progressive dementia + other neuro abnormalities
*Protein: amyloid, tau, synuclein, ubiquitin, huntingtin 3 – Syndrome of disordered posture and movement
4 – Syndrome of progressive ataxia
Degeneration is the process of neuronal, myelin, or tissue breakdown (Phagocytosis and 5 – Syndrome of slowly developing muscular weakness and atrophy
cellular astrogliosis) → affect specific parts of functional NS 6 – Sensory and sensorimotor disorders

Targets of damage: cerebral cortex, motor system, extrapyramidal apparatus, cerebellum *mental → physical → sensory
PROGRESSIVE DEMENTIA
NEUROLOGIC EXAM FINDINGS DEMENTIA WORK-UP (PRIORITY) DEMENTIA WORK-UP (WITH INDICATIONS)
● Aphasia (speech) ● ●
● Apraxia (motor memory) ● ●
● Agnosia (sensory recognition) ● ●
● Executive functioning (complex behavior sequencing)

ALZHEIMER’S DISEASE
EPIDEMIOLOGY CLINICAL MANIFESTATIONS PATHOLOGIC FINDINGS DIAGNOSTIC CRITERIA TREATMENT
- Majority are in their 60s or older EARLY ● Dementia defined by clinical / ●
- 3x higher in women Gross pathology: mental status exam ●
- Autosomal dominant inheritance MODERATE Diffuse brain atrophy ● Patient >40 years old ●
● Deficits in ≥2 areas of cognition
Risk factors: SEVERE Histopathology: and progressive worsening oof
- older, female, - Neurofibrillary tangles memory and other cognitive
- genetic: apoE4 allele COMPLICATIONS → DEATH - Neuritic plaques functions
- metabolic: DM, obesity, - Granulovacuolar degeneration of ● Absence of disturbed
hypertension, high cholesterol neurons (pyramidal layer of consciousness
hippocampus) ● Exclusion of other brain diseases
(e.g., tumor, stroke)
CT and MRI

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Dementia is an acquired, persistent impairment of intellectual function sufficient enough to Classification:

interfere with daily functioning. Cortical Dementia
Subcortical Dementia
Alzheimer’s disease – most common (60%); chronic Toxic Metabolic Dementia
Reversible Dementia
Dementia in the Young
Rapidly Progressive Dementia

UPPER MOTOR NEURON vs LOWER MOTOR NEURON MANIFESTATION

UPPER MOTOR NEURON LOWER MOTOR NEURON
Location CNS: Brain, brainstem, spinal cord PNS: Root, plexus, nerve
Tone Spastic “clasp-knife” Decreased
Reflexes Hyperactive Hypoactive / absent
Babinski’s sign Present Absent
Atrophy None Severe
Fasciculations None Common

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