neurology II

multiple sclerosis

Epidemiology: Young women (20-40 yrs).

Course: Relapsing-remitting (most common) → neurologic deficits separated in time and space.

Optic neuritis (painful vision loss, ↓ color vision).

Internuclear ophthalmoplegia (diplopia).

Sensory changes: paresthesias, numbness.

Motor: weakness, spasticity.

Lhermitte sign: electric shock sensation down spine with neck flexion.

Fatigue, heat sensitivity (Uhthoff phenomenon).

symptoms associated with multiple sclerosis

transverse myelitis

inflammation of the spinal cord

-can occur post-infection, post-vaccination, or with MS/NMO

Acute/subacute motor, sensory, and autonomic dysfunction localized to a spinal cord level.

Bilateral weakness, sensory level, sphincter dysfunction (urinary retention, bowel issues).

symptoms of transverse myelitis

transverse myelitis

Key history clue: rapid onset of bilateral deficits with a clear sensory level.

progressive multifocal leukoencephalopathy

Reactivation of JC virus in immunocompromised (HIV/AIDS, natalizumab, rituximab).

Subacute, progressive neurologic decline (weeks-months).

Cognitive impairment, behavioral changes.

Visual field deficits, ataxia, motor weakness.

symptoms of PM

PML

Key history clue: immunosuppression + progressive multifocal neuro deficits without fever.

Acute disseminated encephalomyelitis (ADEM)

encephalitis in children/young adults often post viral or post-vaccinaation

Monophasic illness (one-time event).

Encephalopathy (confusion, decreased consciousness) + multifocal neuro deficits (weakness, ataxia, vision changes).

symptom of ADEM

Acute disseminated encephalomyelitis (ADEM)

Key history clue: acute, widespread CNS demyelination following infection/vaccine, with encephalopathy.

Campylobacter jejuni, CMV, EBV, Mycoplasma

most common triggers of guillain barre syndrome

Rapidly progressive, symmetric ascending weakness (legs → arms).

Areflexia.

Possible cranial nerve involvement (facial weakness, dysphagia).

Autonomic instability (arrhythmias, BP fluctuations).

symptoms of guillaiin barre syndrome

Guillain-Barre syndrome

Key history clue: acute ascending paralysis after infection.

myasthenia gravis

Epidemiology: Young women, older men; often associated with thymoma or thymic hyperplasia.

Fluctuating weakness, worse with activity, better with rest ("fatigability").

Ocular: ptosis, diplopia (most common presenting).

Bulbar: dysphagia, dysarthria.

Respiratory weakness (myasthenic crisis).

symptoms of myasthenia gravis

myasthenia gravis

Key history clue: weakness that worsens with use, improves with rest.

Etiology: Often paraneoplastic (esp. small cell lung carcinoma).

etiology of lambert eaton myasthenic syndrome

Proximal muscle weakness (legs > arms).

Improves with repeated use (opposite of MG).

Autonomic symptoms: dry mouth, impotence, constipation.

Hyporeflexia.

symptoms of LEMS

Lambert-Eaton myasthenic syndrome

Key history clue: paraneoplastic + weakness improves with activity + autonomic symptoms.

No specific antibody test for MS.

Diagnosis = clinical + MRI + CSF findings.

CSF: Oligoclonal IgG bands (present in >85% of MS patients).

testing diagnostic of MS

JC virus DNA in CSF by PCR.

Antibody testing not used directly for diagnosis (JC virus antibody serology sometimes used to estimate risk in immunosuppressed patients, e.g., natalizumab therapy).

diagnostic testing for PML

Anti-GM1, GD1a, GD1b, GQ1b ganglioside antibodies in certain variants.

antibodies associated with GBS

Anti-acetylcholine receptor (AChR) antibodies (most common).

Anti-MuSK antibodies (muscle-specific kinase) in some seronegative MG patients.

antibodies diagnostic of myasthenia gravis

Anti-VGCC (voltage-gated calcium channel) antibodies

antibodies associated with LEMS

-oligoclonal IgG bands

-elevated IgG index

-normal/mildly elevated protein, normal glucose

CSF findings diagnostic of multiple sclerosis

MRI findings of multiple sclerosis

-white matter lesions hyperintense on T2/FLAIR

-Both enhancing (active, new) and non-enhancing (older) lesions on the same MRI.

-Dissemination in space (lesioins in >2 CNS regions)

-dissemination in time (evidence that lesions occurred at different points in time)

McDonald diagnostic criteria of multiple sclerosis

1st line: IV methylprednisolone

2nd line: plasmapehresis (used for severe rellapses not responding to steroids)

1st and 2nd line management for relapsing MS:

amantadine or modafinil

Rx treatment for the fatigue associataed with MS

gabapentin

tx for neuropathic pain associated with MS

Multiple sclerosis

a chronic, immune-mediated demyelinating disease of the CNS.

The pathology involves autoimmune attack against myelin and, secondarily, axonal injury.

Both innate and adaptive immunity play roles

CD4+ Th1 and Th17 cells cross blood-brain barrier → release cytokines (IFN-γ, IL-17, TNF-α) → activate macrophages & microglia → demyelination.

describe the pathophys of the immune mediated demyeliniation in MS

B cells

which immune cells in MS Produce oligoclonal IgG in CSF, act as antigen-presenting cells, form ectopic follicles in meninges?

Myelin Basic Protein (MBP)

Myelin Oligodendrocyte Glycoprotein (MOG)

Proteolipid Protein (PLP)

what are some of the antibodies that target myellin proteins in MS?

Often triggered by preceding infection (molecular mimicry):

Campylobacter jejuni (most common)

CMV, EBV, Zika, Mycoplasma

what triggers GBS?

Immune response → antibodies cross-react with gangliosides (GM1, GD1a, GQ1b) on peripheral nerves → demyelination ± axonal injury

describe the pathophys of GBS

-ascending symmetric weakness

-hyporeflexia

-mild paresthesias

-facial palsy, dysphagia

symptoms of GBS

Albuminocytologic dissociation → high protein, normal WBC count.

CSF findings associated with GBS

Weakness of diaphragm & intercostal muscles → ventilatory failure.

most common cause of death due to GBS

anti-acetylcholine receptor antibodies aainst post-synaptic NMJ

most common Ab associated with myasthenia gravis

myasthenia gravis

Antibodies block or destroy receptors → impaired neuromuscular transmission → weakness.

Strongly associated with thymic abnormalities (thymoma or thymic hyperplasia)

-fluctuating skeletal m. weakness (worsens with activity)

-ptosis, diplopia

-dysphagia, dysarthriaa

main symptoms of myasthenia gravis

Repetitive nerve stimulation → decremental response

EP findings associated with myasthenia gravis

Ice pack test → improvement of ptosis after application of ice.

Bedside test to aid in diagnosis of myasthenia Gravis

Chest CT/MRI to evaluate for thymoma.

should I get imaging in assessment of MG?

Caused by antibodies against presynaptic P/Q-type voltage-gated calcium channels (VGCCs)

antibodies associated with LEMS

-antibodies against VGCC

Result: ↓ calcium influx into presynaptic terminal → ↓ acetylcholine (ACh) release.

MOA of lambert eaton

-proximal muscle weakness

-autonomic dysfunction: dry mouth, constipation, impotence

-ptosis, diplopia

-hyporeflexia, areflexia

strength improves with repeated activity ("facilitation"), unlike MG.

symptoms of LEMS

Chest CT or PET scan to evaluate for small-cell lung carcinoma

imaging indicated for pts wit LEMS

transverse myelitis

Inflammation across one spinal cord segment → immune-mediated demyelination and axonal injury → sensory, motor, and autonomic dysfunction below the lesion.

CNS white matter

site of PML

JC virus infects and lyses oligodendrocytes → multifocal CNS demyelination. Not antibody-driven, but opportunistic viral-mediated.

pathopys of PMLL

CNS --diffuse white matter

site of ADEM

Widespread perivenular inflammation & demyelination → monophasic encephalopathy with multifocal deficits. Involves T-cell cross-reactivity (molecular mimicry).

pathophys of ADEM

dawson's fingers

In multiple sclerosis, perivascular demyelination creating the appearance of finger projections oriented transversely on an axial scan.

Test for AQP4-IgG, MOG-IgG

antibodies associated with transverse myeliitis

MRI: multifocal asymmetric white matter lesions, no enhancement or mass effect

MRI findings associated with PML

oligodendrocytes

JC virus infects what cells?

HIV work-up, immunosuppression history

lab workup indicatedi n pt diagnosed with PML

ADEM MRI

bilateral symmetric inflammatory changes of the same age

fluffy white spots on T2 weighted

Internuclear ophthalmoplegia

a lesion of the medial longitudinal fasciculus (MLF); disorder of conjugate lateral gaze in which the affected eye fails to adduct when the contralateral eye abducts (w/ nystagmus); most commonly due to MS plaques when presenting in a young person

upper motor neuron signs

spastic paralysis with hyperreflexia, increased muscle tone, positive Babinski sign

upper

is MS associated with upper or lower motor neuron signs?

Bilateral weakness, sensory level, sphincter dysfunction

physical exam findings of transverse myellitis

PML

History: Immunocompromised patient (HIV, natalizumab, transplant), progressive neurologic deficits (aphasia, hemiparesis, vision loss).

ADEM

History: Child/young adult, recent viral illness or vaccination, monophasic acute neurologic deficits + encephalopathy.

Exam: Multifocal deficits, altered mental status.