Neuro: Pathology Flashcards by James Wren

Failure of Rostral Neuropore closure
Characherized by the absence of the Scalp, Skull, and Large portions of the Cortex
Anterior neuropore closure @ day 25
Posterior neuropore closure @ day 27
Increased levels of AFP and ACh

Anencephaly

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Failure of Caudal neopore closure
Severity depends on the degree of closure as well as the location of the Fusion defect
Elevated AFP in Maternal serum or Amniotic fluid

Spina Bifida

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Small Tuft of hair overlying the defect without any visible Herniate contents
Asymptomatic
Missing Lumbar or Sacral processes
Failure of the Vertebral arches to close w/out Herniation of Intraspinal contents

Spina Bifida Occulta

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Protrusion of the Dura mater and Arachnoid, forming a Lumbosacral cyst
Failure of Vertebral arches to close w/ Herniation of Meninges but NOT the Spinal cord

Spina Bifida Meningocele

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Herniated Lumbosacral sac
Depending on the location: Paralysis and Loss of Deep Tendon reflexes and Sensation in the lower extremities as well as Incontinence
A/w Type II Arnold-Chiari syndrome

Spina Bifida Meningomyelocele

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Mental Retardation
Herniation of Meninges and Brain

Spina Bifida Meningoencephalocele

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Herniation of Meninges, Brain, and CSF-containing Ventricles

Spina Bifida Meningohydroencephalocele

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Most severe form of Spina Bifida w/ Myelomeningocele
Flattened plate like mass of nervous tissue w/ no overlying membrane
More prone to life threatening Infections and Meningitis
Split Brain

Spina Bifida w/ Myeloshisis

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Neural tube Birth defect
Posterior Neural tube fails to close by the 27^th day
Vertebrae over defect fail to form and remain Unfused and Open
Spinal cord remains exposed
Motor and Sensory defects
Chronic Infections
Bladder disfunction
A/w Anencephaly

Rachischisis

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Enlarging Head circumference
Dilation of the ventricles (Cranial suture lines not fused)
Congenital Stenosis between 3^rd and 4^th Ventricle
Accumulation of CSF
Common in Newborns

Cerebral Aqueduct Stenosis

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Agenesis / Congenital failure of the Cerebellar Vermis Hypoplasia and Splenium of Corpus Callosum
**Failure ** to Open of the Foramina of Luschka and Foramina of Magendie
Massively dilatated 4^th Ventricle (Posterior fossa) w/out Cerebellum
Accompanied by Hydrocephalus

Dandy-Walker Malformation

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Herniation of the Cerebellar Tonsils ONLY
May not show neurologic symptoms until Adolescens or Adult life
Cerebellar Ataxia
Obstructive Hydrocephalus
Brain stem compression
Syringomyelia
Large Foramen magnum

Arnold-Chiari Type I

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Congenital downward displacement of Cerebellar vermis and Tonsils through the Foramen magnum
A/w obstruction of CSF and Hydrocephalus and Meningomyelocele
Difficulty swallowing (compression of the Nucleus Ambiduus)
Loss of Pain / Temperature sensation along the Back of the Neck and Shoulders
Cranial Nerve and Brain stem dysfunction results in Respiratory failure and Death

Arnold-Chiari Type II

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Cystic degeneration of the Spinal cord
Arises w/ Trauma and A/w Type I Arnold-Chiari malformation, Usually C8 – T1
Sensory (Pain, Temp. Loss) w/ sparing of Fine touch w/ “Cape-like” distribution – Anterior white commissure of the Spinothalamic Tract w/ sparing of the Dorsal column
Muscle atrophy and Weakness – dmg to lower motor neurons of Ant. Horn
A/w Horner Syndrome w/ Ptosis, Miosis, and Anhydrosis

Syringomyelia

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Sympathetic trunk nerves get damaged, same side
Miosis (constricted pupil)
Ptosis (droopy eyelid)
Anhidrosis (decreased sweating)
A/ diseases may be Congential or Acquired

Horner Syndrome

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Dmg to Anterior Motor Horn due to Poliovirus Infection (Piconaviridae Enterovirus)
Fecal-oral transmission
Sore throat, malaise
Lower motor neuron – Flaccid paralysis w/ Muscle atrophy
Fasciculations - small uncontrolled muscle twitch
Weaness w/ decreased Muscle tone
Impaired reflexes
Negative Babinski sign (downgoing toes)

Poliomyelitis

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Inherited degeneration of the Anterior Motor Horn
Autosomal recessive
“Floppy baby”
Death occurs w/in a few years after birth

Werding-Hoffman Disease

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Degenerative disorder of the Upper and Lower motor neurons of the Corticospinal tract - Anterior Horns
Zinc-copper Superoxide Dismutase mutation (SOD1) w/ Familial cases (chrom 21) – free radical injury in neurons
Anterior motor horn degn. – Lower motor neuron signs, Flaccid paralysis w/ muscle atrophy, Fascicultations, Weakness, Impared reflexes, Negative Babinski
Lateral corticospinal tract degn. – Upper motor neuron signs, Spastic paralysis w/ Hyperreflexia, Increased tone, Positive Babinski

Amyotrophic Lateral Sclerosis (ALS)

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Degn. disorder of Cerebellum (Ataxia) and Spinal cord (Loss of Vibratory sense and Proprioception, Muscle weakness in Lower extremities, and loss of Deep tendon reflexes)
Autosomal Recessive – unstable trinucleotide repeat (GAA) in Frataxin gene
Presents in early childhood
Pts. are wheelchair bound w/in a few years
A/w Hypertrophic cardiomyopathy (HCM)
Frataxin – essential for Mitochondrial iron regulation – Free radical damage via Fenton reaction

Friedreich Ataxia

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Group B Streptococci (Streptococcus agalactia)
Listeria monocytogenes
E. coli (Escherichia coli)

Neonatal Meningitis

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Pneumococci (Streptococcus pneumonia)
Meningococci (Neisseria meningitidis)
Influenzae Type B (Haemophilus influenza Type B) (non-vaccinated kids)

Meningitis (6 mos. – 6 yrs.)

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Meningococci (Neisseria meningitidis)
Polio (Picornavirdae enterovirus)
Pneumococci (Streptococcus pneumonia)

Meningitis (6 yrs. 60 yrs)

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Cryptococcosis (Cryptococcus neoformans)

Fungal Meningitis

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Coxsackie A & B (Picornaviridae enterovirus)
Echovirus (Picornaviridae enterovirus B)
Mumps (Paramyxoviridae rubulavirus)
Polio (Picornavirdae enterovirus)

Aseptic Meningitis

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Bacterial Profile of Meningitis?

* Protein: ↑ ↑ * Glucose: ↓ ↓ * Cell Infiltration: Neutrophils and PMNs * Pressure: ↑ * Gram stain and Culture often Identify causative agent

Viral Profile of Meningitis?

* Protein: ↑ or Normal * Glucose: Normal * Cell Infiltration: Lymphocytes w/ normal CSF * Pressure: Normal

Fungal Profile of Meningitis?

* Protein: ↑ * Glucose: ↓ * Cell Infiltration:Lymphocytes * Pressure: ↑

Two Basic Types of Cerebrovascular Disease?

1. Ischemia * Focal * Thrombotic stroke * Embolic stroke * Lacunar stoke * Global 2. Hemorrhage * Intracerebral * Subarachnoid

* Low perfusion (atherosclerosis) * Acute decrease in blood flow (Cardiogenic shock, Overall decrease) - Chronic hypoxia (anemia) * Repeated episodes of Hypoglycemia (Insulinoma) * _Mild_ – Transient confusion w/ prompt recovery * _Moderate_ – Infarcts in watershed areas * Pyramidal neurons of Cerebral cortex – Laminar necrosis * Pyramidal neurons of Hippocampus (Temporal lobe) – long term memory * _Severe_ – Diffuse necrosis w/ ‘vegetative state’

Global Cerebral Ischemia

* Rupture of an Atherosclerotic plaque * Pale infarct at the periphery of the Cortex * Atherosclerosis usually develops at Branch points (Bifurcation of Internal Carotid and Middle cerebral artery, in Circle of Willis)

Thrombotic Stroke

* Due to Thromboemboli * Commonly arising from the Left side of the Heart (Atrial fibrillation) * Usually involves the Middle Cerebral artery * After lysis of Emboli - Hemorrhagic infarct at the Periphery of the Cortex

Embolic Stroke

* Occurs secondary to Hyaline arteriolosclerosis * Complication of **Benign HTN**, **Diabetes mellitus** * Most commonly involves Lenticulostriate vessels, resulting in small cystic areas of infarction * Involvement of the Internal capsule leads to a pure Motor stroke * Involvement of the Thalamus leads to a pure Sensory Stroke

Lacunar Stroke

Progression of Ischemic Stroke?

* **12 hrs** after Infarction: Eosinophilic change in the cytoplasm of neurons (“**Red neurons**”) is an early microscopic finding * **24 hrs** after infarction: * **Neutrophils (days 1 - 3)** * **Microglial cells (days 4 – 7)** * **Gliosis (weeks 2 – 3)** * Formation of Fluid-filled cystic space surrounded by Gliosis – **Caseating necrosis** and **Liquefactive necrosis**

* Bleeding into the Brain parenchyma * Rupture of Charcot-Bouchard microaneurysms of Lenticulostriate vessels – Deep bleeding in Paranchyma of Brain * A/w HTN, reduced HTN decreases incidence by half * Severe Headache, Nausea, Vomiting, and eventual Coma

Intracerebral Hemorrhage

* Bleeding into the Subarachnoid space * Sudden Headache **“Worse Headache of my Life”** w/ **Nuchal rigidity** * Lumbar puncture shows Xanthochromia (yellow hue due to Bilirubin breakdwon) * A/w **Berry aneurysm** – **Saccular (aneurysm) outpouchings** that lack media layer, esp. Anterior Circle of Willis @ branch points of the Anterior communicating artery * A/w Marfan syndrome (FBN1 on Chr. 15 misfolding of Fibrillin-1 – connective tissue weakness) and ADPKD (MVP, Hepatic cysts) * Other causes AV malformations and an Anticoagulated state

Subarachnoid Hemorrhage

* Blood between Dura mater and Skull – bleeding seperates * Fracture of the Temporal bone w/ rupture of the **Middle meningeal artery** * A/w a blow to the head, head trauma * **"Lucid interval"** may precede Neurologic signs * Lens-shaped lesion on CT scan * Herniation – a lethal complication, pushes brain to other side

Epidural Hematoma

* Blood under the Dura mater, covering the surface of the brain * Tearing of Bridging veins that lie between the Dura and Arachnoid * Trauma * Crescent-shaped on CT * Progressive neurologic signs – leading toward Herniation (lethal) * Increased rate in Elderly due to age-related cerebral atrophy, stretching the veins

Subdural Hematoma

* Displacement of the cerebellar tonsils into the Foramen magnum * Compression of the Brain stem leads to Cardiopulmonary arrest

Tonsillar Herniation

* Displacement of the Cingulate gyrus under the Falx cerebri * Compression of the Anterior cerebral artery leads to infarction

Subfalcine Herniation

* Displacement of the Temporal lobe uncus under the Tentorium cerebelli * Compression of CN III (oculomotor) leads to the eye moving “down and out” and a Dilated pupil * Compression of Posterior cerebral artery leads to Infarction of Occipital lobe (Contralateral homonymous hemianopsia) * Rupture of the Paramedian artery leads to Duret (brainstem) hemorrhage

Uncal Herniation

* Autosomal recessive lysosomal storage disease * **Arylsulfatase A Deficiency** (Autosomal recessive) * Most common Leukodystrophy * Sulfatides cannot be degraded and Accumulate in the Lysosome of Oligodendrocytes (lysosomal storage disease) -\> impaired production of myelin sheath * Central and Peripheral Demyelination w/ **Ataxia** and **Dementia** * **Accumulation of Sulfatides**

Metachromatic Leukodystrophies

* Autosomal recessive Lysosomal Storage dieseae * **Deficiency of Galactocerebrosidase** * Galactocerebroside and Psychosine destroy myelin sheath, accumulates in Macrophages * Peripheral neuropathy * Developmental delay * Optic atrophy * Globoid cells

Krabbe disease

* Mostly **Males** * Impaired Metabolism and addition of **Coenzyme A** to **Long-chain Fatty-acids** (**X-linked defect**) * **Accumulation** of **Fatty-acids** damages **Adrenal glands** (Adrenal gland crisis) and **White matter** of the **Brain** * **Long-term progression **-\> **Death**

Adrenoleukodystrophy

* **Autoimmune inflammation** / destruction of **CNS** myelin and Oligodendrocytes (**demyelination**) * Chronic CNS disease of Young Women (20 – 30 yrs old) (F \> M) - **Brain** and **Spinal cord** * A/w HLA-DR2 * Regions away from Equator * Blurred vision in ONE eye (optic nerve) (**Marcus Gunn pupils**) * Vertigo and Scanning speech mimicking Alcohol intoxication (Brain stem) * Internuclear ophthalmoplegia (medial longitudinal fasciculus) * Hemiparesis or Unilateral loss of sensation (cerebral white matter) * Lower extremeity loss of sensation (spinal cord) * **Bowel, Bladder, and Sexual dysfunction** (ANS) * Dx: MRI and Lumbar puncture (increased Lymphocytes, Immunoglobulins w/ Oligoclonal IgG bands, Myelin basic protein) * Gray appearing plaques in White matter * Tx: Acute: IV Solumedrol, Chronic: High-dose steroids, and Long-term β-INF

Multiple Sclerosis Charcot classic triad of MS is a **SIN** * **S**canning speech * **I**ntention tremor (also **I**ncontinence and Internuclear ophthalmoplegia) * **N**ystagmus (involuntary eye movement)

* Progressive, Debilitating encephalitis – Leads to Death * Slowly progressive * Persistent infection of the Brain by Measles virus (Paramyxoviridae Morbillivirus – Rubeola, Togaviridae Rubivirus – German Measles - Rubella) * Infection occurs in Infancy – Neurologic signs arise years later (during childhood) * Viral inclusions w/in Neurons (gray matter) and Oligodendrocytes (white matter)

Subacute Sclerosisng Panencephalitis

* **JC virus** infection of Oligodendrocytes (white matter) at multiple foci (Papovaviridae Polyomavirus) * **Immunosuppression** (**AIDS** or **Leukemia**) leads to reactivation of the Latent virus * Demyelination of CNS due to destruction of Oligodendrocytes * Presents w/ **Rapidly progressive** neurologic signs (visual loss, Weakness, Dementia) which **leads to Death**

Progressive Multifocal Leukoencephalopathy

* Focal demyelination of the Pons (Anterior Brain stem) * Due to rapid intravenous correction of Hyponatremia (alcoholic) * Severly malnourished pts. (Liver disease) * Presents as Acute bilateral paralysis “Locked-In” Syndrome * Loss of voluntary movement from head to toe, but can still move eyes

Central Pontine Myelinolysis

* Degenerative disease of Cortex, **↓ ACh** * **Widespread cortical atrophy** * **Narrowing Gyri** and **Widening Sulci** * Slow-onset memory loss and Progressive disorientation * Loss of learned Motor skills and Language * Changes in Behaviour and Personality * Patients become Mute and Bedridden * Infection is common cause of Death * **Risk increases w/ Age** * E4 allele of Apolipoprotein E (**ApoE4**) a/w increased Risk on **Chrom 19, ApoE2 on Chr. 19 is protective** * E2 allele w/ decreased Risk * Familial cases a/w Presenilin 1 (**Chrom 14) **and Presenilin 2 (**Chrom 1**) mutations * A/w **Down syndrome by age 40** due to **p-APP** on **Chrom 21** * Cerebral atrophy, **Neuritic 'Senile' plaques**, AB amyloid (APP) chromosome 21 * **Neurofibrillary tangles** – aggregates of fibers Hyperphosphorylated Tau Protein * Loss of Cholinergic neurons in the Nucleus Basalis of Meynert * **Senile plaques**: extracellular **β-amyloid core**; may cause amyloid angiography → Intracranial hemorrhage * αβ-amyloid syn. by cleaving the precursor APP

Alzheimer Disease (AD)

* Consequene of Moderate Global Ischemia * Multifocal infarction and Injury due to Hypertension, Atherosclerosis, or Vasculitis * 2^nd most common cause of dementia

Vascular Dementia

* Frontotemporal atrophy * Dementia, Aphasia, Parkinsonian aspects, Change in personality * Degenerative disease of the Frontal and Temporal Cortex * Spares the Parietal and Occipital lobes and Posterior 2/3 of Superior temporal gyrus * **Round aggregates of Tau protein (Pick bodies)** in neurons of the Cortex * Behavioral and Language symptoms aries early; progress to dementia

Pick Disease | (frontotemporal dementia)

* Degenerative loss of Dopaminergic neurons (**Dopamine-secreting**) **pigmented neurons** in the **Substantia nigra** of the Basal ganglia (**Midbrain**) * Nigrostriatal pathway of Basal ganglia uses Dopamine to initiate movement * α-synuclein, parkin, DJ-1, and PINK1 genes and proteins * Aging, rare cases a/w MPTP exposure * “TRAPS” – Tremor, Rigidity, Akinesia/bradykinesia (exp.less face), Postural instability, Shuffling gait * Pigmented neurons in the Substantia nigra and Round, Eosinophilic inclusions of alpha-synucleain (**Lewy bodies** – Hallucinations) * '**Pill-rolling**' tremor

Parkinson Disease

* Degeneration of GABAergic neurons in the Caudate nucleus of the Basal ganglia – Inhibitory neural transmitter * Loss of Spiny striated neurons that normally dampen motor activity * **Autosomal Dominant** disorder (Chromsome 4p16) * Trinucleotide repeat (CAG) in huntingtin gene (40 - 55, 70+), Normal (6 - 34 repeats) * Repeats during Spermatogenesis leads to Anticipation * **Chorea (snake-like) movements** progress to **Dementia** and **Depression** * **~40 years old** * Suicide is common cause of death

Huntington Disease

* Increased CSF – Dilated Ventricles * Dementia in Adults (Idopathic) * Triad – Urinary incontinence, Gait instability, Dementia (“Wet, Wobbly, Wacky”) * Lumbar puncture improves symptoms * Tx: Ventriculoperitoneal shunting

Normal Pressure Hydrocephalus

* Degenerative Prion protein disease * PrP^C-\> PrP^SC (Beta pleated sheet) * Sporadic conversion * Inherited Familial forms * Transmitted * Pathologic protein not degradable * Intracellular vacuoles dmgs. Neurons and Glial cells

Spongiform Encephalopathy

* **Rapidly progressive Dementia** (weeks to months) w/ **Myoclonus** ("startle myoclonus") * Most common **spongiform encephalopathy** * Sporadis, rarely arises due to exposure * Rapidly progressive **Dementia a/w Ataxia** (cerebellar involvement) and Startle myoclonus (involuntary contractile w/ sensation) * **Hallucinations** followed by **Parkinsonian features** * Sharp waves seen on EEG * Death w/in 1 year

Creutzfeldt-Jakob disease (CJD)

* An inherited form of prion disease characterized by: * Severe Insomnia * Exaggerated Startle Response

Familial Fatal Insomnia

* Malignant, high-grade **Tumor of Astocytes** * Most common CNS tumor in Adults * **Cerebral Hemisphere**, **Crosses the Corpus callosum** * **“Butterfly”** lesion * Regions of necrosis surrounded by tumor cells ‘**pseudopalisadin**g’ and Endothelial cell proliferation * Pleomorphic Tumor cells (astrocytes) are **GFAP positive** * Poor prognosis (~1 year survival)

Glioblastoma Multiforme (GBM)

* Bening 1^• tumor of Arachnoid cells, Brain Tumor * Most common **benign CNS** tumor in adults * More commonly seen in **Women** (presents w/ **Estrogen receptors**), and rare in children * Seizures; tumor compresses but DOES NOT invade the Cortex * Convexities of Hemispheres, near Brain surface * May have Dural attachment "**Dural Tail**" * Round mass **attached to the Dura** on imaging -\> presses **on the Cortex** -\> causes seizures * ‘**Whorled pattern**’ w/ **Psammoma bodies** on histology w/ **Pink cytoplasm**

Meningioma

* Bening tumor of **Schwann cells (PNS)** * Involves Cranial or Spinal nerves; w/in the Cranium * **Most commonly** seen in **CN VIII** at the **Cerebellopontine angle** * Loss of hearing and Tinnitus – ‘ringing in the ears’ -\> Acoustic schwannoma (aka acoustic neuroma) * Tumor cells are **S-100 positive** * **Multiple pigminted skin lesions** and **Optic nerve glioma** a/w Neurofibromatosis Type 1 * Bilat. Tumor cells seen in Neurofibromatosis Type 2 (**NF-2**) * Tx: Stereotactic radiosurgery

Schwannoma

* Malignant tumor of Oligodendrocytes * Imaging reveals a **Calcified tumor** in the White matter * Usually involving the **Frontal lobe** * May present w/ Seizures * '**Chicken-wire**' capillary pattern * ‘**Fried-egg**’ apperance of cells on biopsy - round nuclei w/ clear cytoplasm

Oligodendroglioma

* **Benign tumor of Astrocytes, **good prognosis * Most common **CNS** tumor in Children * **Usually** arises in the **Cerebellum (Posterior Fossa**) * Cystic lesion w/ **Mural nodule** on imaging, **Well circumscribed **(Cystic + solid (gross)) * **GFAP positive** * Rosenthal fibers (thick corkscrew Eosinophilic processes of Astrocytes) on Biopsy

Pilocytic Astrocytoma

* **Malignant tumor** derived from the **Granular cells** of the **Cerebellum midline** (Neuroectoderm) * Usually arises in Children * **Small, Round Blue cells**; **Homer-Wright rosettes** may be present: small cells wrap around neurotic proccess * Tumor grows **Rapidly** and spreads via CSF * Metastasis to the Cauda equina is termed ‘**Drop metastasis**’ -\> Spinal cord * Can compress 4th ventricle -\> Hydrocephalus * Poor prognosis

Medulloblastoma

* **Malignant** tumor of **Ependymal cells** * Usually seen in Children * Most commonly arises in the **4^th Ventricle** * May present w/ **Hydrocephalus** -\> beneath the Tentorium – blocking CSF flow in CNS * **Perivascular Pseudorosettes** are characteristic finding on biopsy * **Calcification **is common (**Tooth enamel-like**)

Ependymoma

* **Benign Childhood tumor** arises from Epithelial remnants of **Rathke’s pouch** (Surface ectoderm Anterior pituitary) * **Supratentorial tumor** mass in Children and Young Adult * Compress the **Optic chiasm** -\> Bitemporal hemianopsia (a/w tumors of pituitary) * **‘Tooth-like’ Calcifications** * Tends to recur after Resection

Craniopharyngioma

* Initially dementia and Visual hallucinations followed by **Parkinsonian features** * **Progressive Cognitive decline** similar to Alzheimer disease * α-synuclein defect

Lewy Body Dementia

* Most common varieant of Guillain-Barre syndrome * Autoimmune against Schwann cells -\> Inflammation and Demyelination of PNS and motor fibers * Ascending muscle weakness / paralysis beginning in the lower extremities * Facial paralyis (50%) * Increased CSF protein w/ normal cell count (albuminocytologic dissociation) * Increased protein -\> Papilledema * A/w Campylobacter jejuni and CMV -\> autoimmune attack of peripheral myelin due to molecular mimicry inoculations, and stress * No definitive link to pathogens

Acute Inflammatory Demyelinating Polyradiculopathy

* Multifocal perivenular Inflammation and Demyelination after infection (commonly Measles or VZV) or certain vaccines (e.g. Rabies, Smallpox)

Acute Disseminated (Post-infectious) Encephalomyelitis

* a.k.a **Hereditary Motor and Sensory neuropathy (HMSN)** * Group of progressive hereditary nerve disorders related to the defective production of **Proteins** involved in the **Structure** and **Function** of **Peripheral nerves** of the **Myelin Sheath** * Typically Autosomal dominant pattern * A/w **Scoliosis** and **Foot deformities** (High and Flat arches)

Charcot-Marie-Tooth Disease

* Affect 1 area of the Brain * Most commonly originate in Medial Temporal Lobe * Often preceded by Seizure aura * **Simple, Partial** - (consciousness intact) - motor sensory, autonomic, psychic * **Complex, Partial** - (impaired consciousness)

Partial (focal) Seizures

* **Absence** (petit mal) - 3 Hz, no postictal confusion, blank stare * **Myoclonic** - quick, repetitive jerks * **Tonic-clonic** - (grand mal) - alternating stiffening and movement * **Tonic** - stiffening * **Atonic** - "drop" seizures (falls to floor); commonly mistaken for fainting

Generalized Seizures

* Most often composed of Stromal cells in small blood vessels w/in **Cerebellum, Brain Stem, and Spinal cord** * A/w **von Hippel-Lindau Syndrome** when found w/ **Retinal agiomas** * Due to ectopic production of Erythropoietin can lead to -\> A/w 2^• **Polycythemia** (paraneoplastic syndrome = increased RBC count) * Closely arranged * Thin walled capillariey w/ minimal Paranchyma composed of Endothelial cells, Pericytes, and Stromal cells

Hemangioblastoma

* Most commonly **Prolactinoma** * Bitemporal **Hemianopia** (**decreased vision or blindness**), Vertigo, Nausea, Vomiting * Amenorrhea, Galactorrhea (Increased milk production - women) * Sexual dysfunction, Hypogonadism, Gynocomastia (men) * Shows normal visual field above, patient's perspective below) due to **Pressure** on **Optic Chiasm** * **Hyper-** or **Hypo-Pituitarism** are sequelae

Pituitary Adenoma

* **Vitamin B1 (Thiamine) deficiency** * Uncommon in individuals w/ varied diet * A/w **Chronic alcoholism** * Capillary proliferation, Hemorrhage, Necrosis, and **Hemosiderin** deposition are often found in the **Mammillary bodies** and the Periaqueductal gray matter * Results in **Paralysis** of **Extraocular muscles**

Wernicke-Korsakoff disease

* Diverticulum of malformed brain tissue extending through a defect in the Cranium * Most often occurs in the Posterior Fossa * Comparable extensions of brain occur through the Cribiform plate in the Anterior Fossa ("sometimes misleadingly referred to as a "Nasal Glioma")

Encephalocele

* Abnormal generation and migration of Neurons results in **malformations** of the **Forebrain** that may be focal or involve entire structures * **Small Head Circumferance** * A/w **Chromosome abnormalities**, **Fetal Alcohol syndrome**, **HIV-1** infection in utero * Reduction in the number of neurons that reach the Neocortex leads to a **Simplification of the Gyral Folding**

Microcephaly

* **Bilateral optic neuritis** and **Spinal cord demyelination** * **Anti-bodies (Ab)** against **Aquaporin-4**, the major protein in **Astrocytes** and areas of demyelination * Loss of Aquaporin-4 * Ab injure through **Complement-dependent** mechanisms * White cells are common in **CSF** (including **Neutrophils**) * Vascular **deposition** of **Immunoglobulin** and **Complement** * Tx: reduce Ab burden, Plasmapheresis, Depletion of B cells w/ anti-CD20 Ab

Neuromyelitis Optica

* gene 178 of PrP^c * gene 129 of PrP^c * homozygotes Met/Met at gene 129 of PrP^c

Prion Proteins * gene 178 of PrP^c = Fatal Familial Insomnia (Asp) --\> results in encoding Metionine at 129 * gene 129 of PrP^c = Famiial Forms (Met or Val) * Homozygous Met/Met = Creuzfeldt-Jakob Varient

* Degeneration of Frontal and/or Temporal Lobes * Alterations in personality, behavior and language (aphasias) precede memory loss * Global dementia and Early onset Dementia * A/w Cellular Inclusions of FTLD-tau and w/ TDP43 (FTLD-TDP) found in the nucleus (phosphorylated and ubiquitinated)

Frontaltemporal Lobe Dementia

* Accumulation of Storage Material w/in Neurons --\> followed by death of the Neurons * Seizures, Generalized loss of Neurologic function

Neuronal Storage Disease

* G_m2 gangliosidoses a lysosomal storage diseases caused by an inability to Catabolize G_m2 gangliosides * Accumulates in the Heart, Liver, Spleen, Nervous System * Central and Autonomic nervous systems and Retina dominate the clinical picture * Cherry-red spot thus appears in the Macula * Cytoplasmic inclusions w/ Onion-skin layers * Mutations in the α-subunit locus on chromosome 15 causes a severe deficiency of Hexosaminidase A * Ashkenazic Jews (1:30)

Tay Sachs Disease

* Rare disorder in which Lipid pigments accumulate in Neurons * Neuronal dysfunction leads to a combination of Blindness, Cognitive, and Motor Deterioration and Seizures.

Ceroid Lipofuscinosis

* Impared oxygen-carrying capacity of Hemoglobin * CO interactions w/ Cytochrome C oxidase inhibiting electron transport in mitochondria * Selective injury to layers III and V of Cerebral cortex, Sommer center of the Hippocampus, and Purkinje cells * **Bilateral necrosis of the Globus Pallidus** * Demyelination of White matter tracts as Late event

Carbon Monoxide Poisoning (CO)

* Preferentially affects the Retina; degeneration of Retinal Ganglion cells causes Blindness * Bilateral necrosis of the Putamen and Focal White-matter necrosis also occur when the exposure is severe * Disruption of Oxidative phosphorylation and Nonenzymatic protein modification * Ingestion of illicit liquor (moonshine)

Methanol Poisoning

* Degeneration of both Ascending and Descending Spinal tracts * Defect in Myelin formation * Bilateral symmetrical Numbness, Tingling, and slight Ataxia in the Lower Extremities * Complete Paraplegia may occur * Starts in the Mid-Thoracic level * Swelling in Myelin layers produces vacuoles, with eventual Axon degeneration

Vitamin B₁₂ Defeciency

* Wernicke Encephalopathy - acute appearance of a combination of psychotic symptoms and Opthalmoplegia * Acute symptoms are reversible when treated w/ Thiamine --\> if untreated results in Korsakoff syndrome * **Disturbances in Short-term memory (MedialDorsal Lesions in Thalamus) and Confabulation** * Common in Chronic Alcoholism * Focal hemorhage and necrosis in the Mamillary bodies and the walls of the 3rd and 4th Ventricles * Development of Cystic space w/ Hemosiderin-laden Macrophages

Thiamine Deficiency

Aβ Protein

Alzheimer Disease

Tau Protein

* Alzheimer Disease * Frontotemporal lobar degeneration * Parkinson Disease w/ LRRX2 mutations * Progressive supranuclear palsy * Corticobasal degeneration

TDP-43 Protein

* Frontotemporal lobar degeneration * Amyotrophic lateral sclerosis (ALS)

FUS protein

* Frontotemporal lobar degeneration * Amyotrophic lateral sclerosis

α - synuclein Protein

* Parkinson Disease * Multiple system atrophy

Polyglutamine Aggregates

* Huntington Disease * Spinocerebellar Ataxia (some forms) * Spinal Bulbar Muscular Atrophy

Neuro: Pathology Flashcards

(93 cards)