Vascular dementia:

• Caused by damage to the blood vessels supplying the brain — most often from a prior stroke or from chronic ischemia (reduced cerebral blood flow).
• The textbook's causes list (Box 17.2) names three vascular sources: multi-infarct brain lesions (multiple small strokes), a single focal infarct, and Binswanger disease — a rare diffuse white-matter disease from arteriosclerosis and thromboembolism affecting the vessels that supply the white matter, basal ganglia, and thalamus.
• The week 7 webinar frames the mechanism as repeated, sometimes silent, ischemic events: each stroke or TIA can leave damage even without symptoms at the time, and the damage accumulates. Net effect: reduced blood supply → ischemic damage → cell death → gradual cognitive decline, typically hitting memory, executive function, and problem-solving.

Frontotemporal dementia (FTD):

• Caused by progressive degeneration (atrophy) of the frontal and temporal lobes — the regions that govern personality, behavior, and language.
• Table 17.14 identifies behavioral-variant FTD's molecular drivers as mutations in MAPT (the tau gene) and progranulin (PGRN), both on chromosome 17, each accounting for roughly 10% of familial cases; the resulting pathology is tau inclusions, Pick bodies, and neurofibrillary tangles.
• The week 7 webinar also names TDP-43 as an abnormal protein that can build up in FTD alongside tau — this protein is not named in the assigned textbook excerpt.
• In people younger than 60, FTD rivals Alzheimer disease in frequency — it is not the rare disease its overall prevalence suggests.

Vascular dementia (Table 17.15):

Frontotemporal dementia (Table 17.15) — two clinical variants:

Neurologic exam in FTD often shows parkinsonism — changes in walking or movement can present first — most associated with the CBD (corticobasal degeneration) and PSP (progressive supranuclear palsy) variants of the disease.

Two forms, split by age of onset:

Down syndrome (trisomy 21) carries a high incidence of early-onset AD, because the APP gene sits on chromosome 21; many affected individuals develop AD by age 40, with clinical signs before 65.

The shared pathologic cascade, once either pathway starts:

1. Faulty processing and clearance of amyloid precursor protein (APP) leaves toxic amyloid-beta fragments behind.
2. Those fragments aggregate into extracellular neuritic (beta-amyloid) plaques, disrupting nerve impulse transmission.
3. Tau protein becomes hyperphosphorylated and forms intraneuronal neurofibrillary tangles.
4. Basal forebrain cholinergic neurons degenerate, cutting acetylcholine output — the week 7 webinar extends this to say acetylcholine, glutamate, and serotonin levels are all disrupted, affecting memory, cognition, and mood.
5. Neurons lose synaptic plasticity and die; the cerebral cortex — especially the hippocampus and temporal lobes — progressively atrophies.

Amyloid-beta doesn't stay confined to neurons — it also deposits in blood vessels:

Amyloid-beta deposits in the smooth muscle of cerebral arteries, producing amyloid angiopathy and chronic brain hypoperfusion, which itself contributes to neurodegeneration — one reason differentiating AD from vascular dementia can be difficult in some patients.

An emerging mechanism — the oral/gut microbiome:

The textbook's Emerging Science box links chronic periodontitis to AD: toxins from Porphyromonas gingivalis and related bacteria are thought to damage the blood-brain barrier and promote neuroinflammation, amyloid deposition, and tau phosphorylation. Swallowed oral bacteria can also trigger gut inflammation that raises intestinal permeability, letting inflammatory mediators reach the bloodstream, breach a leaky blood-brain barrier, and add to neuroinflammation.

Demographic risk factors:

• Age — onset is usually between 20 and 40 years old.
• Sex — MS is more common in women; men who develop it tend to have a more severe, progressive course.
• Geography — prevalence is higher in northern latitudes and in areas with less sun exposure.

Gene–environment risk factors the textbook itself flags as inconclusive (studied, not proven):

• Genetic susceptibility — MS is an autoimmune response to self or microbial antigens that occurs specifically in genetically susceptible individuals.
• Smoking
• Vitamin D deficiency
• Obesity
• Epstein-Barr virus (EBV) infection

The etiology of MS is unknown. Life expectancy is not greatly shortened by the disease, and the course often extends over 30 years.

GBS is a rare demyelinating disorder caused by a humoral (antibody) and cell-mediated immune reaction against the peripheral nerves. Two subtypes: acute inflammatory demyelinating polyneuropathy (AIDP), the demyelinating form, and acute motor axonal neuropathy (AMAN), the axonal form — AMAN notably has no sensory involvement, since cross-reactive antibodies target axonal gangliosides at the nodes of Ranvier.

GBS usually occurs within 4 weeks after a respiratory or gastrointestinal infection, and has been linked to surgery, immunization, immune checkpoint inhibitors, and infections including Campylobacter jejuni, Zika virus, and SARS-CoV-2.

Clinical manifestations, in ascending order:

• Tingling and weakness, progressing to ascending flaccid paralysis starting in the legs
• Progression to complete quadriplegia
• Respiratory insufficiency
• Autonomic nervous system instability — low blood pressure and arrhythmias

Treatment: IV immunoglobulin or plasmapheresis during the acute phase, respiratory support as needed, followed by aggressive rehabilitation. Recovery occurs over weeks to up to 2 years; approximately 20% of individuals have residual weakness.

How the antibodies cause weakness:

• Autoantibodies destroy AChR sites through antibody-mediated complement activation, forming a membrane attack complex — or they simply block ACh from attaching to the receptor.
• Either way, transmission of the nerve impulse across the NMJ is diminished. Muscle depolarization is incomplete or unsuccessful, which is what produces muscle weakness — consistent with the week 7 webinar's summary: an autoimmune attack on AChRs at the NMJ.

The thymus's role:

• Thymic abnormalities are common — hyperplasia of germinal centers, where T cells interact with B cells to produce the autoantibodies.
• About 10%-20% of people with MG develop thymoma; about 30% of people with thymoma develop MG.

Not everyone with MG has AChR antibodies:

• About 10%-15% of people with MG test negative for AChR antibodies but have MuSK antibodies (an IgG4 subtype) instead. This is a distinct subtype — not complement-mediated — more common in women in their 40s.
• Other antibody subgroups target LRP4 or agrin, both components of MuSK receptor function.

The cause of the underlying breakdown in self-tolerance that starts this autoimmune process is unknown.

The hallmark pattern both sources agree on:

• Fatigable, fluctuating weakness that worsens with activity/exertion and improves with rest — it is not constant, not steadily progressive without remission, and not worse specifically in the morning.

Muscle groups, in the order the textbook says they're typically affected:

• Ocular — ptosis (drooping eyelid) and diplopia (double vision) are usually first; the extraocular and eyelid muscles have the fewest AChR sites, so they're affected earliest.
• Bulbar/facial — facial weakness (an expressionless face), difficulty chewing and swallowing, drooling, and a nasal, low-volume, high-pitched monotonous speech.
• Neck, shoulder girdle, hip flexors — less frequently affected; fatigue after exercise, with possible progressive weakness.
• Respiratory — diaphragm and chest-wall weakness with impaired ventilation; the most dangerous stage, risking myasthenic crisis (extreme weakness, respiratory insufficiency, danger of respiratory arrest).

Two named variants (week 7 webinar, slide 36):

• Ocular MG — limited to the eye muscles only.
• Generalized MG — spreads beyond the eyes to face, throat, and limbs.

Don't confuse the two crises. Myasthenic crisis is severe generalized weakness with respiratory insufficiency, from the disease itself. Cholinergic crisis looks similar but comes from anticholinesterase drug toxicity, follows the medication by 30-60 minutes, and adds smooth-muscle overactivity — diarrhea, intestinal cramping, bradycardia, pupillary constriction, increased salivation, diaphoresis. Both carry a danger of respiratory arrest.

Four processes drive peripheral nerve damage (week 7 webinar, slide 58; McCance Ch. 18):

• Axonal degeneration — from metabolic failure within the axon or vascular ischemia (e.g., diabetes, toxins); distal axon degenerates first, then myelin, giving a "stocking-glove" pattern
• Demyelination — axon spared, only myelin degenerates (e.g., Guillain-Barré syndrome, per the webinar)
• Inflammation — autoimmune neuropathies (e.g., lupus, rheumatoid arthritis)
• Ischemia — vasculitic neuropathy, from inadequate blood flow/oxygen to the nerve

A separate process, wallerian degeneration, is distinct from the above: the axon and myelin distal to a site of traumatic axonal interruption degenerate — characteristic of a severed nerve, not of metabolic or ischemic injury.

Electromyography (EMG), nerve conduction studies, and imaging help differentiate axonal from demyelinating neuropathies. Management targets the underlying cause — e.g., glucose control in diabetic neuropathy — plus symptom management (gabapentin, pregabalin, duloxetine, amitriptyline for pain), avoiding alcohol, nutritional support, and foot care.

Per the textbook, axonal degeneration — the same process seen in diabetic neuropathy — can be caused by metabolic failure within the axon or by vascular ischemia. When ischemia is the driver, the distal axon degenerates first, followed by the myelin, producing the same "stocking-glove" pattern of sensory/motor loss.

The week 7 webinar names this cause vasculitic neuropathy (slide 58) and, in the transcript, describes it as numbness and tingling because the extremity is "not getting enough oxygen."

The textbook's parallel category is a vascular (hypoxemia) cause of a patchy, multiple-mononeuropathy (multiplex) distribution, usually tied to an underlying systemic disease: diabetes mellitus, vasculitis, or lupus erythematosus.

Evaluation and treatment follow the general neuropathy workup — clinical history, EMG, nerve conduction studies, and imaging — directed at identifying and controlling the underlying vascular or systemic cause.

Bacterial meningitis is primarily an infection of the pia mater, arachnoid villi, subarachnoid space, ventricular system, and CSF. The most common pathogens in adults are Streptococcus pneumoniae, Haemophilus influenzae type b, and Neisseria meningitidis. It spreads by respiratory droplets and contact with contaminated saliva or respiratory secretions.

Clinical manifestations group into three categories:

• Infectious signs — fever, tachycardia, chills
• Meningeal signs — severe throbbing headache, severe photophobia, nuchal rigidity, positive Kernig and Brudzinski signs
• Neurologic signs — decreased consciousness, cranial nerve palsies, focal deficits (hemiparesis/hemiplegia, ataxia), seizures; often projectile vomiting; papilledema as ICP rises, progressing to delirium and possibly unconsciousness and death

With meningococcal meningitis, a petechial or purpuric rash covers the skin and mucous membranes. A rare complication is purpura fulminans — bacterial endotoxin and inflammatory cytokines cause a rapidly progressive hemorrhagic skin infarction with disseminated intravascular coagulation, which can lead to multi-organ failure, ischemic necrosis of digits/limbs requiring amputation, and death.

Evaluation and treatment: rapid diagnosis, antibiotic administration, and supportive care are critical. Diagnosis relies on physical exam, blood cultures, nasopharyngeal smear/antigen tests, and CSF analysis/culture. Vaccines exist for meningococcal, pneumococcal, and H. influenzae meningitis.