A 32-year-old woman presents with a 3-month history of intermittent blurred vision and problems walking. The patient states that she often feels “pins and needles” in her legs that cause her problems when she’s walking. The patient is afebrile, and her vital signs are within normal limits. An autoimmune disorder is suspected. Which of the following findings would most likely be present in this patient?

Damaged myelin sheath and myelin-producing cells

Destruction of blood-brain barrier

Degeneration of anterior horn cells

Decreased cerebrospinal fluid due to destruction of cells

A 29-year-old woman presents with progressive vision loss in her right eye and periorbital pain for 5 days. She says that she has also noticed weakness, numbness, and tingling in her left leg. Her vital signs are within normal limits. Neurological examination shows gait imbalance, positive Babinski reflexes, bilateral spasticity, and exaggerated deep tendon reflexes in the lower extremities bilaterally. FLAIR MRI is obtained and is shown in the image. Which of the following is the most likely cause of this patient’s condition?

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)

A 35-year-old woman with a history of Crohn disease presents for a follow-up appointment. She says that lately, she has started to notice difficulty walking. She says that some of her friends have joked that she appears to be walking as if she was drunk. Past medical history is significant for Crohn disease diagnosed 2 years ago, managed with natalizumab for the past year because her intestinal symptoms have become severe and unresponsive to other therapies. On physical examination, there is gait and limb ataxia present. Strength is 4/5 in the right upper limb. A T1/T2 MRI of the brain is ordered and is shown. Which of the following is the most likely diagnosis?

Sporadic Creutzfeldt-Jakob disease (sCJD)

Variant Creutzfeldt-Jakob disease (vCJD)

Subacute sclerosing panencephalitis (SSPE)

A 38-year-old woman comes to the physician for a follow-up examination. Two years ago, she was diagnosed with multiple sclerosis. Three weeks ago, she was admitted and treated for right lower leg weakness with high-dose methylprednisone for 5 days. She has had 4 exacerbations over the past 6 months. Current medications include interferon beta and a multivitamin. Her temperature is 37°C (98.6°F), pulse is 90/min, and blood pressure is 116/74 mm Hg. Examination shows pallor of the right optic disk. Neurologic examination shows no focal findings. She is anxious about the number of exacerbations and repeated hospitalizations. She is counseled about the second-line treatment options available to her. She consents to treatment with natalizumab. However, she has read online about its adverse effects and is concerned. This patient is at increased risk for which of the following complications?

Syndrome of inappropriate antidiuretic hormone

A 43-year-old man presents to the emergency department following a work-related accident in which both arms were amputated. The patient lost a substantial amount of blood prior to arrival, and his bleeding is difficult to control due to arterial damage and wound contamination with debris. His complete blood count (CBC) is significant for a hemoglobin (Hgb) level of 5.3 g/dL. The trauma surgery resident initiates the massive transfusion protocol and orders whole blood, O negative, which she explains is the universal donor. The patient receives 6 units of O negative blood prior to admission. He subsequently develops fever, chills, hematuria, and pulmonary edema. Several hours later, the patient goes into hemodynamic shock requiring the emergent administration of vasopressors. Of the following options, which hypersensitivity reaction occurred?

Type 2 hypersensitivity reaction

Type 1 hypersensitivity reaction

Combined type 1 and type 4 hypersensitivity reaction

Type 3 hypersensitivity reaction

Type 4 hypersensitivity reaction

A 61-year-old woman comes to the physician because of a constant, dull headache and generalized body pains for the past 8 months. She has also had difficulty hearing from her left side, which started a month after the onset of the headaches. Five months ago, she had surgery to correct a fracture of the right femur that occurred without a fall or any significant trauma. Five years ago, she underwent a total thyroidectomy for localized thyroid carcinoma. She takes levothyroxine and calcium supplements, which she started after menopause. Physical examination reveals a prominent forehead and irregular, tender skull surface. Bony tenderness is present over bilateral hip and knee joints, with decreased range of motion of the right hip joint and increased anterior curvature of both tibias. Laboratory studies show a highly elevated level of alkaline phosphatase, with vitamin D, calcium and PTH levels within normal limits. A plain x-ray of the head is most likely to show which of the following findings?

Mixed lytic and sclerotic lesions

Periosteal trabeculations with radiolucent marrow hyperplasia

Generalized dense, sclerotic bone

Multiple, well-defined, punched out lytic lesions

Lytic lesions with no sclerotic margin

Demyelinating diseases for USMLE Step 3: High-Yield Pathology Lessons

Demyelination - Myelin Under Attack

Autoimmune-mediated destruction of the myelin sheath, which slows or blocks nerve impulse conduction.
Central (CNS): Oligodendrocytes are the primary target. Key diseases include Multiple Sclerosis (MS) and Progressive Multifocal Leukoencephalopathy (PML).
Peripheral (PNS): Schwann cells are attacked. The classic example is Guillain-Barré Syndrome (GBS).

⭐ In MS, MRI reveals characteristic demyelinating plaques, often in a periventricular distribution.

Multiple Sclerosis - Plaques on the Brain

Grossly visible, demyelinated lesions in the CNS white matter. They represent the focal endpoint of the inflammatory cascade in MS.

MRI brain T2-FLAIR: MS periventricular/juxtacortical plaques

Key Features & Evolution:
- Acute (Active) Plaques: Pink, edematous, ill-defined. Contain perivascular lymphocytes and lipid-laden macrophages (myelin breakdown).
- Chronic (Inactive) Plaques: Gray/tan, firm, sharply demarcated (sclerotic). Characterized by astrocytic proliferation (gliosis) and an absence of myelin.

Classic Locations:
- Periventricular white matter (Dawson's fingers)
- Juxtacortical
- Infratentorial (brainstem, cerebellum)
- Spinal cord

⭐ High-Yield: Plaques often have a characteristic ovoid shape and are oriented perpendicular to the lateral ventricles, following the path of deep medullary veins. This is the basis for the classic "Dawson's fingers" sign on sagittal MRI.

MS Differentials - Mimics & Variants

Inflammatory/Post-infectious
- ADEM (Acute Disseminated Encephalomyelitis): Monophasic, post-infectious/vaccination, affects children.
- NMOSD (Neuromyelitis Optica): Relapsing; targets optic nerves & spinal cord. AQP4-IgG positive.
- Neurosarcoidosis: Granulomatous inflammation; cranial neuropathies, leptomeningeal enhancement.
Infectious
- PML (Progressive Multifocal Leukoencephalopathy): JC virus in immunosuppressed (HIV, natalizumab).
- Lyme Neuroborreliosis: Borrelia burgdorferi; facial palsy, radiculoneuritis.

MRI of demyelinating diseases: MS, NMOSD, and ADEM lesions

⭐ NMO Spectrum Disorder (NMOSD) is distinguished from MS by the presence of Aquaporin-4 antibodies (AQP4-IgG), which are highly specific and target astrocytic foot processes.

MS Variants (Fulminant)
- Marburg Type: Acute, monophasic, severe course with large lesions.
- Balo's Concentric Sclerosis: Lamellar, onion-like rings of demyelination.

Guillain-Barré Syndrome - Crawling Paralysis

Pathogenesis: Acute, immune-mediated inflammatory polyneuropathy causing demyelination of peripheral nerves. Frequently triggered by infections (Campylobacter jejuni, CMV) through molecular mimicry.
Clinical: Classic presentation is a rapidly ascending, symmetric paralysis.
- Starts in lower extremities, progressing upwards over days to weeks.
- Key sign: Areflexia or marked hyporeflexia.
- May involve cranial nerves and respiratory muscles.
- Autonomic dysfunction (tachycardia, BP instability) is common.
Diagnosis:
- CSF: Albuminocytologic dissociation (↑↑ protein, normal WBC count).
- EMG/NCS: Markedly slowed nerve conduction velocity.
Treatment: IV immunoglobulins (IVIG) or plasmapheresis.

⭐ Exam Favorite: The most life-threatening complication is respiratory failure from paralysis of the diaphragm and intercostal muscles.

📌 Mnemonic: Ground-to-Brain Syndrome.

Guillain-Barré Syndrome Symptoms

High‑Yield Points - ⚡ Biggest Takeaways

Multiple Sclerosis (MS) is an autoimmune CNS disease with periventricular plaques and oligoclonal bands in the CSF.

Guillain-Barré Syndrome (GBS) is a PNS condition, often post-infectious, causing ascending paralysis with albuminocytologic dissociation in CSF.

Progressive Multifocal Leukoencephalopathy (PML) results from JC virus in the immunosuppressed, leading to widespread CNS demyelination.

Charcot-Marie-Tooth is a hereditary PNS neuropathy causing distal muscle weakness and high-arched feet.

Acute Disseminated Encephalomyelitis (ADEM) is a post-infectious CNS demyelination, primarily in children.

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