Diseases Flashcards
Guillain-Barre syndrome (Acute inflamamtory demyelinating polyradiculopathy)
Location: peripheral nerves
Pathogenesis: immune mediated disorder initiated by infection or immunization-Abs cross react with myelin on spinal root and peripheral nerves
Endoneural inflammatory infiltration
SEGMENTAL DEMYELINATION
Presentation: ascending paralysis with weakness in distal limbs rapidly advancing to proximal muscles, slowed nerve conduction velocity, variable autonomic dysfunction, sensory signs, muscle weakness and arreflexia
Antecedent infection-Campylobacter, CMV, Orthomyxo, other GI infections
Pathology: chronic inflammation, segmental demyelination
Pathogenesis: T cell mediated immune response, demyelination by activated macrophages
Findings: increased CSF protein with norma cell count
increased protein count leads to papilledema
Treatment: supportive therapy (Respiratory support is critical) and immunimodulatory therapy
No onion bulb
Spinal muscular atrophy
Weeding Hoffman disease SMA type 1
Age: birth to first 4 months
Location: degeneration of LMNs, congenital degeneration of anterior horns
Autosomal Recessive
Presentation: expected LMN dysfunction, muscle weakness, hypotonia, muscle wasting and tongue fasciculations “floppy baby”
Median age is 7 months
ALS
Age: middle aged and elderly
Location: degeneration of LMNs and UMNs
CST and peripheral nerves occurs with neuronal degeneration
Pathogenesis: unknown 10% familial with autosomal dominance gene encoding for superoxide dismutase
Presentation: symptoms of upper motor neuron dysfunction and LMN dysfunction
Gross pathology: atrophy of anterior horn cells in spinal cord; wallerian degeneration, demyleniation of corticospinal tracts
Loss of neurons in motor nuclei of CN V, IX, X, XII
Effect: denervation atrophy of muscles, mild atrophy of precentral gyrus
Presents as fasciculations with eventual atrophy and weakness of hands
Treatment: riluzole
Respiratory complications are most common cause of death
Charcot Marie tooth disease
Age: childhood, early adulthood
Location: peripheral nerves
Inheritance: autosomal dominant
Pathogenesis: duplication on chromosome 17 gene for peripheral myelin protein 22 involved in function of peripheral nerves or myelin sheath
Presentation: distal muscle weakness, atrophy of perineal muscle leads to inverted champagne bottle lower extremities, sensory deficits, slowly progressive, hammertoes, high arch, palpable nerve enlargement, tremor
Pathology: segmental demyelination and remyelination with onion bulb formation, hypertrophic neuropathy
No specific treatments
Diabetic neuropathy
Symmetric distal polyneuropathy pain and parenthesis as in lower limbs
Predominant sensory deficits
Pathology: nonspecific axonal loss, hyalinization of vessel walls
Pathogenesis: hyperglycemia causes non enzymatic glycosylation of proteins, lipids, and nucleic acids
May interfere with normal protein function and activate inflammatory signaling
Intracellular glucose reduced to sorbitol which depletes NADPH and increases osmolality predisposing peripheral nerves to reactive oxygen species
Treatment: manage diabetes
Myasthenia gravis
Immune mediated loss of ACh receptors on post synaptic terminal
Decrement in motor responses with repeated stimulation
Nerve conduction studies are normal
Presentation starts with extraocular muscle weakness and generalized weakness worsens with exertion
Thymic abnormalities
Antibodies for ACh receptors present
Multiple sclerosis
Age: 20-50 years more common in women
Genetic factor is HLA-DR2, environmental factor is being away from the equator
Pathogenesis: immune system contributes to demyelination, and neurodegeneration autoimmune self myelin antigens. Infiltrates of plaques consist of T cells and macrophages
Impaired saltatory conduction
Gross pathology: plaques of demyelination in white matter of brain and spinal cord located next to lateral ventricles best seen on FLAIR imaging
Loss of myelin and oligodendrocytes in plaques and reactive gliosis (astrocytosis)
Lipid laden macrophages contain products of myelin breakdown
Diagnosis: clinical history, MRI, & CSF analysis
Active lesions have gadolinium enhancing lesion MRI shows gray plaques in white matter
CSF has increased lymphocytes and gamma globulin in IgG bands
Clinical: remitting and relapsing, optic neuritis is common initial symptom, demyelination of MLF is common-conjugate eye movements, scanning speech, bowel, bladder and sexual dysfunction, intention tremor, incontinence, cerebellar dysfunction
Insensitivity to heat
Treatment: IFN beta 1b (betaseron) IFN beta 1a (avonex) inhibit IFN gamma activity, COP1 (copaxone) inhibits immune response to myelin basic protein, acute attacks use high dose steroids
Central pontine myelinolysis
Demyelination in the basis pontis and pontine tegmentum.
Associated rapid correction of hyponatremia
Changes in osmolality damage oligodendrocytes
Occurs in malnourished patients (alcoholics or liver disease)
Symptoms: rapidly evolving quadriplegia or locked in syndrome
Acute paralysis, dysarthia, dysphagia, diplopia and loss of consciousness
Secondary to osmotic forces and edema
Metachromatic leukodystrophy
Deficiency of lysosomal enzyme arylsulfatase A
Autosomal recessive
Accumulation of sulfatides
Inhibits differentiation of oligodendrocytes and eliciting a pro inflammatory response from microglia and astrocytes impairing production of myelin sheath
Findings: central and peripheral demyelination with ataxia and dementia
Demyelination with gliosis
Metachromic material found in urine
Adrenoleukodystrophy
Mutations In members of ATP binding cassette transporter family of proteins
X linked recessive
Inability to catabolism very long chain fatty acids so higher levels in serum
Progressive loss of myelin and adrenal insufficiency behavioral problems in young males
Fatal
Amyloid neuropathy
Selective pain and temperature abnormalities and autonomic dysfunctions
Associated with cardiac myopathy and renal diseases
Loss of small axons, endonurial/peri vascular amyloid deposits
Pathogenesis: mutations of transthyretin
Treatment: pacing and renal dialysis
Liver transposition arrests progression
Leprosy
Clinical: slow symmetrical polyneuropathy affecting pain fibers, affect extremities with lower temp
Lepromatous: widespread infection of Schwann cells and skin
Tuberculoid: granulomatous inflammation in endoneurium, epineurium and dermis
Pathology: granulomatous inflammation, segmental demyelination and axonal loss,endonurial fibrosis and thickening of perineurial sheath
Diphtheria
Clinical: parathesias and weakness with early loss proprieception and vibratory sensation
Pathology: nonspecific axonal and myelin loss
Pathogenesis: corynebacterium diphtheria exotoxins blocks protein synthesis
Treat the infection
Varicella-zoster/shingles
Clinical: painful vesicular eruption and neuropathy involving localized dermatome in adult and elderly patients
Pathology: nonspecific axonal loss, neuronal loss in ganglia
Pathogenesis: reactivation of varicella
Treatment: supportive therapy and vaccine
Uremic neuropathy
Distal sensorimotor polyneuropathy caused by uremic toxins
Correlated with renal insufficiency
Dying back or central peripheral axonopathy
General intracranial pressure increase
> 200 mm water in lumbar puncture
Speed of expansion and age of patient affect severity
Clinical features: headache, nausea/vomiting, decreased level of consciousness
Papilledema
Causes: hemorrhage, neoplasm, infection, edema, hydrocephalus
Treatment: hyperventilating a patient to ensure adequate oxygenation, administering IV mannitol to create hypertonic solution within blood to decrease fluid content of neurons, administering steroids
Cingulate gyrus herniation
Cingulate gyrus herniates under the falx cerebri
Affects: autonomics, mood, limbic system
Clinical features not measurable
Can compress ACA
Uncal herniation
Uncus (medial temporal lobe) herniates across tentorium cerebelli to compress structures in posterior fossa
Compression of contralateral cerebral peduncle, hemiparesis ipsilateral to side of herniation referred to as kernohan’s notch or quadriplegia
Affects ipsilateral midbrain-contra lateral hemiparesis and hyperflexia
pons/brainstem-duret hemorrhages can lead to death, respiratory, postural and occulomotor changes
Medulla-slow irregular respirations, irregular pulse and falling blood pressure, death may occur
Compresses ipsilateral cranial nerve III-occult motor defects, pupillary dilation (first sign and can become bilateral), no constriction, ptosis, eye lateral and down
posterior cerebral artery-ischemia/hemorrhagic infarction to ipsilateral occipital lobe causing contralateral homonymous hemianopsia
Bilaterally causes cortical blindness-patient doesn’t comprehend visual images but pupillary reflexes are intact
Cerebellar tonsil herniation
Goes through foramen magnum
Compresses medullary respiratory centers leading to death
Midline shift
Lateral displacement of diencephalon may produce decreased level of consciousness
Central herniation (rostral caudal deterioration)
Progressive decline in neurological status due to downward displacement of the diencephalon, midbrain, pons and medulla
Changes in: consciousness (reticular activating system), respiration (medulla), postural reflexes-decorticating and decerebrate, pupils
Diencephalon lesion: small reactive pupils
Midbrain lesion: midsized and fixed pupils (both symp and para affected)
Abducens nerve palsy
Elevated ICPncan result in downward displacement of the brainstem-stretching the abductees nerve
CN VI has the longest subarachnoid course
Clinical presentation: diplopia, ipsilateral or contralateral paralysis of lateral gaze
Parinaud syndrome
Caused by hydrocephalus and pineal gland tumors-germinomas (superior colliculus)
Abnormalities of eye movement and pupil dysfunction
Paralysis of upward gaze and convergence
Hydrocephalus
Accumulation of excessive CSF within the ventricular system of the brain
Enlarges head if before sutures close
Intracranial pressure increased if not-papilledema or herniation
Non communicating: obstruction of CSF flow within ventricular system at outlet foramina. Sites of narrowing are commonly obstructed-arnold chiari or dandy walker
Communicating: obstruction of CSF flow in subarachnoid space after exit from fourth ventricle-caused by leptomeningitis and subarachnoid hemmorhage-ventricles symmetrically enlarged
Therapy: shunting the CSF and reestablishing flow
Epidural hemmorhage
Results from tearing of MMA causing bleeding that dissects the dura from the inner table of skull
Associated with skull fracture often of the temporal bone-pterion (facture at frontal, parietal, temporal and sphenoid-bone is thin and MMA courses within the skull at this point)
MMA is branch of maxillary artery (of external carotid) enters skull via foramen spinosum
Rapidly space occupying lesion death occurs 2-12 hours after injury
Causes uncal herniation/ transtentorial herniation and/or downward displacement of brainstem can cause CN III palsy
Clinical: Initial unconsciousness followed by lucid interval (seconds to hours) progression to coma
Symptoms: focal signs and indications of increases intracranial pressure, less alertness, contralateral hemiparesis and ipsilateral pupillary dilation
Imaging: biconvex high density, sharply defined, rarely crosses Sutural margins, may cross midline
Between dura and bone
Subarachnoid hemorrhage
Accompanied by cerebral contusion-worst headache of my life
Bloody or yellow CSF may be detected 2-3 days later (xanthochromic)
Bleeding raised from small vessels
Bruising associated with fracture of the skull
Hydrocephalus may result if subarachnoid bleeding or fibrosis obstructs CSF flow
Associated with Marfan, Ehlers Danlos, ADPKD, coarctation of the aorta or an AVM of posterior and anterior communicating arteries
Risks:
vasospasm due to blood breakdown-new onset ischemia, confusion and focal signs-diagnose with transcranial doppler and treat with nimodipine
Rebleeding-re development of severe headache, nausea, vomiting, change in consciousness new neurlogical deficits-diagnose with CT
Can have blood in basal cisterns
also have nuchal rigidity and fever (watch out for meningitis)
Between arachnoid and pia
Concussion
Head injury that may cause unconsciousness, respiratory arrest and loss of reflexes
Instantaneous onset
Change in momentum of the head is thought to be a critical factor in producing a concussion
No parenchymal abnormalities on CT
Contusion
Area of hemorrhagic necrosis
Following a head injury the brain strikes supporting structures and bony projections of skull bruising gyral crests
Location: frontal lone orbital surfaces and temporal lobes are most common
Produced by rotation of the brain or by linear forces
Can be coup or contrecoup lesions
Pathology: summit of gyrus is smashed, lesion is wedge shaped with base towards the pia and apex towards white matter, in early stages the hemorrhage remains bright red an surrounding tissue is edematous later becomes brick red and finally orange brown due to deposition of Hemosiderin
Dura-arachnoidal adhesions form on the surface and frequently cause post traumatic epilepsy
Imaging: high density areas on CT
Cauda equina syndrome
Acute loss of function of the nerve roots in the Cauda equina usually due to tumor, trauma, herniated lumbar disk (pudendal nerve)
Patients present with lower extremity weakness and sensory loss and bowel and bladder incontinence
low back pain, saddle anesthesia, loss of anocutaneous reflex, loss of ankle jerk reflex, with plantar flexion weakness
Best assessed by MRI
Neurosurgical or radiation therapy emergency
Cataract
painless Opacity of normally clear lens which may develop as a result of aging, metabolic disorders, trauma or hereditary, smoking, alcohol, excessive sunlight, prolonged corticosteroid use, classic galactosemia, galactokinase deficiency, diabetes (sorbitol), trauma, infection
Optic neuritis
Rapid onset of central vision loss most present with ocular pain made worse when moving the eye Affects women and Caucasians more Mean age is 32 Treat with IV corticosteroid Use MRI to determine risk of MS
Acute pyogenic meningitis
Presents with: nuchal rigidity, photophobia, and headache
Purulent exudate in subarachnoid space and along vessels, include neutrophils and bacteria
Inflammatory infiltrate in walls of arteries
Cellular infiltration of CNs and spinal roots
Edema could occur in brain tissue
CSF is a sensitive indicator: high pressure (>200), decreases glucose, increased protein, thousands of neutrophils
Hyperintensity in sulci and cisterns on FLAIR imaging
Acute lymphocytic meningitis
Presents with: confusion, headaches, photophobia
Viral meningitis
Mononuclear exudate
CSF indicator: normal or slightly increased pressure, normal glucose, mildly increased proteins, hundreds of mononuclear cells
Hyperintensity in sulci and cisterns on FLAIR imaging
Arthropod-borne viral encephalitis
Most common epidemic viral encephalitis often in tropical climates
Caused by arboviruses generally
Animal hosts and mosquito vectors
Affects cortex and basal ganglia but can vary
Herpes simplex virus type 1 encephalitis
Most common non epidemic form of encephalitis
High mortality levels
Acyclovir is an effective treatment
Symptoms: alterations in mood, memory and behavior due to lesions in the limbic system
Lesions involve the inferior and medial regions of the temporal lobes and the orbital gyri of frontal lobes-MRI
Necrosis and hemorrhagic regions
Peri vascular infiltrates and inclusion bodies are present
Diagnosis:PCR of CSF to detect viral DNA
Often RBCs are present in CSF due to necrotizing pathology
Herpes simplex virus type 2 encephalitis
Affects the nervous system
In adults generally causes meningitis
Neonates can acquire infection from mom an develop encephalitis
Varicella zoster virus encephalitis
Causes chickenpox in primary infection
Establish latent infection in sensory neurons of dorsal root or trigeminal ganglia
Reactivation results in painful vesicular skin eruption in dermatome
Can cause granulomatous arteritis may cause infarcts
Immunosuppressive patients can develop encephalitis or myelitis
Cytomegalovirus encephalitis
Infects the nervous system of fetuses or immunocompromised individuals
Opportunistic pathogen in AIDs patients
Poliomyelitis encephalitis
Infects anterior horn neurons in spinal cord causing motor defects and flaccid paralysis
Post polio syndrome can occur after the initial infection up to 20 years later
Caused by poliovirus (enterovirus) spread fecal-orally
Replicates in oropharynx and small intestine before sperading via bloodstream to the CNS
Symptoms: LMN lesion and infection signs
Findings: CSF with increased WBCs and slight increase of protein (no CSF glucose change)
Virus recovered from stool or throat
Live attenuated vaccine produces a strong mucosal secretory IgA response (offers protection at the site of viral entry by inhibiting attachment to intestinal epithelial cells)
Rabies
Bite of rabid animal
Enters CNS by ascent of peripheral nerves
Negritos bodies present in pyramidal neurons of hippocampus
Intracerebral abscesses
Usually caused by pyogenic bacteria:strep and staph
Fungi may produce localized areas of intracerebral inflammation termed granulomatous in immunosuppressed
Discrete lesions with central liquefactive necrosis, surrounded by inflammatory cells and fibrous tissue, proliferation of small blood vessels, vasogenic edema, fibrolats are recruited, reactive gliosis
CSF changes: increased pressure, relatively few cells, mildly elevated white cell count and protein level, normal glucose
Clinical: progressive focal deficits, general signs of intracranial pressure
Ependymitis and meningitis occur
Seizures in approx 50% of cases
3 types of neurosyphilis
All have increases cell count and positive serologic reaction in CSF (VDRL/RPL)
1. Meningovasculitis: infiltration of meninges and vessels by lymphocytes and plasma cells, causes symptoms similar to meningitis or stroke
- General paresis: atrophy, loss of cortical neurons especially in frontal lobes, gliosis, proliferation of micro glial cells, peri vascular lymphocytes and plasma cells, spirochetes in brain tissue.
Symptoms: Mental changes, dementia and headache - Tabes dorsalis: inflammatory lesions involving meninges and vessels in subarachnoid space of dorsal nerve roots. Loss of axons and myelin in dorsal roots with wallerian degeneration of dorsal columns
Symptoms: lightning pains, sensory deficits, loss of pain sensation and loss of position sense leads to ataxia, argyll Robertson pupils (react to accommodation -constrict to nearby objects but not light)
Symptoms: progressive ataxia, arefelxia and loss of bladder function (due to spirochetes damaging midbrain tectum)
HIV associated dementia
50-70% of aids patients develop
Cognitive. Motor and behavioral dysfunction including mood disturbances
HIV association dementia located in sub cortical areas sparing the cerebral cortex
Microscopic changes: diffuse white pallor, peri vascular infiltrates of lymphocytes and macrophages, foci of necrosis, gliosis and/ or demyelination, micro glial nodules macrophages and multinucleated giant cells
Virus enters brain via macrophages
Neuronal injury occurs via secretion of cytokines and Chemokines
Vacuolae myelopathy in the spinal cord in the posterior and lateral columns
Progressive multifocal leukoencepnalopathy
Occurs in patients with associated immune suppression or chronic disease
Fifth and sixth decades of life
Symptoms: Intellectual deterioration and dementia. Also cortical visual symptoms, motor disorders, abnormal movements
Death in 2-6 months
Normal CSF findings
Pathogenesis: Slowly progressive viral encephalitis by JC polymavirus
Infections occur during childhood and are largely asymptomatic, persist in kidneys and lymphocytes
Restricts replication to glial cells and infects OLIGODENDROCYTES causing demyelination
Gross pathology: widespread demyelination
Microscopic pathology: inclusion bodies in oligodendroglia nuclei, transformed bizarre astrocytes and gliosis, lesions primarily in sub cortical white matter but also occur in brainstem and cerebellum
increased risk associated with natalizumab
Polyomavirus: Naked,, DS DNA circular
Subacute sclerosing panencephalitis
Progressive encephalitis associated with altered measles virus
Onset: 5-20 years occurs in children of young adults . Early age infection with measles
Clinical: progressive personality changes, intellectual deterioration, seizures, spasticity of limbs
Duration: death in years
CSF changes: elevated IgG and antibody tiger against measles is elevated
Pathogenesis: persistent nonproductive infection of CNS
Microscopic changes: inclusion bodies in oligodendroglia, neurons and astrocytes. Peri vascular cuffing by lymphocytes and plasma cells, paramyxovirus nucleocapsid tubules characteristic of measles in inclusion bodies
Anencephaly
Absence of brain of all parts except basal ganglia, brainstem and cerebellum
Open calvarium
Increased alpha fetoprotein
Polyhydramnios (no swallowing center in brain)
Associated with maternal diabetes type I
Failure of anterior neuro pore to close
Occurs with raschischis which is the failure of Vertebral canal to fuse
Folate supplementation decreases risk
Meningomyelocele
Meninges and spinal cord protrude through defect in vertebral column
Most lumbosacral
Accompanying hydrocephalus and Arnold chiari malformation (downward displacement of cerebellum tonsils through foramen magnum causing non communicating hydrocephalus
Non lethal-most common
Encephalocele
Meninges and brain tissue protrude through a skull defect
Midline
