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The usual initial complaint is a specific muscle weakness rather than generalized weakness
Extraocular muscle weakness or ptosis is present initially in 50% of patients and occurs during the course of illness in 90%
The disease remains exclusively ocular in only 16% of patients
Rarely, patients have generalized weakness without ocular muscle weakness
Bulbar muscle weakness is also common, along with weakness of head extension and flexion
Limb weakness may be more severe proximally than distally
Isolated limb muscle weakness is the presenting symptom in fewer than 10% of patients
Weakness is typically least severe in the morning and worsens as the day progresses
Weakness is increased by exertion and alleviated by rest
Weakness progresses from mild to more severe over weeks or months, with exacerbations and remissions
Weakness tends to spread from the ocular to facial to bulbar muscles and then to truncal and limb muscles
About 87% of patients have generalized disease within 13 months after onset
Less often, symptoms may remain limited to the extraocular and eyelid muscles for years

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Pathology and pathophysiology

Midbrain atrophy

Hummingbird sign in MRI midsaggital plain - preserved pons, atrophied midbrain

Neurofibrillary tangles

Abnormally phosphorylated tau protein → accumulate → deterioration of brain cells

Reduction in GABAergic basal ganglia output neuron (dopaminergic modulation) - poor response to dopaminergic therapy

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Key clinical features

Unsteady walking and frequent unexplained falls, mainly backward

Stiffness of the neck > limbs

Visual problems – an inability or reduced ability to look up or down, light sensitivity, slow blinking of eyelids and difficulty maintaining eye contact

Slow, slurred quiet speech

Difficulty swallowing

Slowness of movements generally

Risk Factors

AGE (mean age of onset 62)

Possible environmental exposure (phosphate, chromate ore - in France)

Possible genetic susceptibility - microtubule-associated protein tau gene (MAPT) - over abundance of tau protein

Clinical predictors of short survival

onset of fall during the first year

early dysphagia

early incontinence

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How MG symptoms progress?
The disease frequently presents (40%) with only ocular symptoms. However, the extraocular almost always are involved within the first year. Of patients who show only ocular involvement at the onset of MG, only 16% still have exclusively ocular disease at the end of 2 years.
In patients with generalized weakness, the nadir of maximal weakness usually is reached within the first 3 years of the disease. As a result, half of the disease-related mortality also occurs during this period. Those who survive the first 3 years of disease usually achieve a steady state or improve. Worsening of disease is uncommon after 3 years.

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https://docs.google.com/presentation/d/1K_TgGqAR3MVcPz2d7PM1Qto9xB9gIOg8V11CSdSCCJ0/edit?usp=sharing

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What is the classification of MG?
Class Description
I Any eye muscle weakness, possible ptosis, no other evidence of muscle weakness elsewhere
II Eye muscle weakness of any severity, mild weakness of other muscles
IIa Predominantly limb or axial muscles
IIb Predominantly bulbar and/or respiratory muscles
III Eye muscle weakness of any severity, moderate weakness of other muscles
IIIa Predominantly limb or axial muscles
IIIb Predominantly bulbar and/or respiratory muscles
IV Eye muscle weakness of any severity, severe weakness of other muscles
IVa Predominantly limb or axial muscles
IVb Predominantly bulbar and/or respiratory muscles
V Intubation needed to maintain airway
Physical examination

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Glioblastoma, also known as glioblastoma multiforme (GBM), is the most aggressive cancer that begins within the brain.

1. Primary GBM
-60% of cases, >50y.o.
-present after a short clinical Hx, usu <3mths
-de novo: w/o evidence of pre-existing tumor
2. Secondary GBM
-40%, < 45y.o.
-malignant progression from low-grade astrocytma/ anaplastic  astrocytoma
-time of progression varies from <1yr - >10yrs, mean interval 4-5 yrs

Risk factors include:

Sex: male (slightly more common in men than women) [Male]

Age: over 50 years old [65 y.o.]

Ethnicity: Caucasians, Hispanics, and Asians

Signs and symptoms of glioblastoma are initially non-specific.

Signs and symptoms

The clinical history of a patient with glioblastoma multiforme (GBM) is usually short (<3 months in >50% of patients). Common presenting symptoms include the following:

Slowly progressive neurologic deficit, usually motor weakness

Headache

Generalized symptoms of increased intracranial pressure, including headaches, nausea and vomiting, and cognitive impairment

Seizures

Neurologic symptoms and signs can be either general or focal and reflect the location of the tumor, as follows:

General symptoms: Headaches, nausea and vomiting, personality changes, and slowing of cognitive function International

Focal signs: Hemiparesis, sensory loss, visual loss, aphasia, and others

Morning Headache?

Glioblastoma takes up space in brain and causes increase in ICP. Headache may then occur. It is worse in the morning because patients have laid down the night before.

Lung cancer relation?

About half of metastatic brain tumors are from lung cancer.

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What is the prognosis?
With treatment, most individuals with myasthenia can significantly improve their muscle weakness and lead normal or nearly normal lives. Some cases of myasthenia gravis may go into remission—either temporarily or permanently—and muscle weakness may disappear completely so that medications can be discontinued.

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What is the differential diagnosis of Parkinson's disease and PSP?

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Hi

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See you all on Friday!