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
Heterotopias
Clusters of neurons in abnormal locations
Associated with seizure disorder
Can be in cerebellum and dentate nucleus
Failure of migration of nerve cells from sub ependymal region to cortex
Holoprosencephaly
Cerebral hemispheres fail to divide properly (malformation)
Most sporadic but can have autosomal dominant inheritance
One mutation involves sonic hedgehog gene- which produces intercellular signaling
Moderate=cleft lip/palate, Severe=cyclops
Associated with trisomy 13, 18 and consequence of Fetal Alcohol syndrome
Arnold chiari malformation
Type II: Herniation of cerebellar tonsils and vermis through foramen magnum
Defect in neural tube closure
Small posterior fossa
Misshapen midline cerebellum
Elongation of medulla pons and 4th ventricle
Kinking medulla (difficulty swallowing, dysphonia, stridor and apnea)
Malformation of colliculi
Acqueductal stenosis leads to hydrocephalus
Associated with meningomyeolocele and hydrocephalus (can lead to mental impairment)
Type I:low lying cerebellar tonsils extend below the forament magnum into vertebral canal
Asymptomatic in infants adults have headaches and ataxia
Associated with syringomyelia
Dandy walker malformation
Large posterior fossa
Malformation of cerebellum vermis with midline cyst replacing vermis
Lateral displacement of cerebellar hemispheres by enlarged 4th ventricle
Hydrocephalus in forebrain
Lined by ependymal and arachnoid mater
Associated with spina bifida
Cerebral palsy
Not a specific disease entity
Non progressive motor deficit
90% congenital; 1/3 premature
10% acquired
Pathology: hemmorhages and infarctions, may occur in white matter of hemispheres, may result in weakness or movement disorders
Causes: prenatal and perinatal infection, trauma, asphyxia, maternal high BP or diabetes, hemorrhages and infarcts
Diagnosis: does not hit milestones after birth, difficulty in maintaining body temp, extreme irratiablity, frequent gagging
Management: maximize functional abilities of patients
Types:
Spastic-most common, increased tone, jerky movements, more severe in lower limbs than in upper limbs. Cross over gait
Ataxic- incoordination, imbalance, poor muscle tone, unsteady and shaky
Athetoid: involuntary movements, difficulty maintaining posture, irregular movements of face, upper body and arms
Hyperbilirubinemia is a common cause
Tay-Sachs disease
Neuronal storage disease
Prevalent among Ashkenazic Jews
Deficiency if hexosaminidase A
Accumulation of GM2 gangliosides
Onset: 3-8 months
Clinical: seizures, exaggerated startle reflex, macular cherry red spot, motor incoordination, mental deterioration
1-2 years vegetative state is reached and death at 2-3 years
Pathology: lysosomal storage vacuoles in neurons, ballooned cell body, primarily in gray matter
Krabbe disease
AR Neuronal storage disease
Deficiency of galactocerebroside B-galactosidase
Accumulation of psychosine and galactocerebroside
Onset: 3-6 months
Clinical: motor deterioration, feeding difficulties, seizures, crying, irritability, optic atrophy
Pathology: decreased myelin in CNS and peripheral nerves
Globoid cells
Loss of white matter
Friedreich Ataxia
Most common inherited ataxia-Autosomal recessive
GAA repeat expansion in an intron-Frataxin gene (Iron binding protein)-unstable triplet repeat associated with IMM-mitochondrial impairment
Onset: 2-16 years
Lesions in DRG dorsal columns, spino cerebellum tracts
95% clumsiness is first sign Dysarthria follows
55% pes cavus deformity,
otherwise, weakness, sensory loss in limbs, cardiac hypertrophy (CHF and arrhythmias cause of death) and skeletal abnormalities (kyphoscoloiosis), loss of deep tendon reflexes
Atrophy of spinal cord
Loss of axons and myelin in posterior columns, spinocrebellar tracts and corticospinal tracts
Degeneration of the cerebellar dentate nucleus
Diabetes mellitus can develop
Metachromatic leukodystrophy
Deficiency of arylsulfatase A
Accumulation of sulfatides
Onset: late infantile most common
Clinical: progressive mental and motor deterioration, peripheral neuropathy
Pathology: widespread myelin deficit in white matter
Leukocoria
White pupil
No red reflex
Infantile cataract most common
Can be hereditary, trauma, metabolic error
Interrupts normal process of visual development
Obtain dilated fundus exam for retinoblastoma diagnosis
Dyskinesias
Uncontrolled arm and leg movements
Excessive dopamine stimulation in diseased brain
Linked to each dose of levodopa
Treatement: reduce levodopa dose, add dopamine agonist, amantidine, deep brain stimulation to pallidum and subthalamic nucleus
Normal pressure hydrocephalus
Secondary Parkinsonism
Wet wobbly and wacky
Communicating hydrocephalus-expansion of ventricles disorts the fibers of corona radiata
Gait disturbance and incontinence (occur first due to traction of sacral motor fibers-distinguishes from Alzheimers)
Short term memory loss and emotional blunting (due to disension of periventricular limbic system)
Enlarged ventricles-due to gradual decline in resorptive capacity of arachnoid villi with slow CSF accumulation
can be reversed
Parkinson’s disease
Progressive neurodegenerative disorder
Onset: middle to old age
4 cardinal features: resting tremor, bradykinesia, rigidity, gait instability ASYMMETRICAL (TRAP)
Impaired function of nigrostriatal dopamine neurons
Non-motor features: mood disorder, dementia and dysautonomia, impaired function on non dopamine neurons
Olfactory dysfunction, constipation and sleep disorders occur before motor deficits
Pathology: degeneration of pigmented brainstem neurons-substantia nigra, Lewy bodies in neurons (round eosinophilic and filled with a-synuclein, reduced) brain decreased dopamine in striatum
Epi: second most common progressive neuro degenerative illness, slightly more common in men
Risk factors: age, severe head trauma, family history, exposure to pesticides, well water, rural living, heavy metals, Von economos encephalitis, MPTP and low uric acid
Treatment: levodopa/Caribidopa, dopamine agonists, MAO-B inhibitor maybe amantidine and anticholinergics
Progression: slowly worse, motor fluctuations, dyskinesia
Corticabasal degeneration
Akinetic rigid syndrome Asymmetric rigidity Apraxia Myoclonus Alien limb Rare, gaze palsy
Progressive supranuclear palsy
Akinetic rigid syndrome confused with Parkinson’s
Rapid, Early falls, down gaze paresis, axial rigidity, truncal apraxia, wide eyed unblinking face, executive function loss
males more often affected
Only 20% respond to levodopa
Pathology: accumulation of hyper-phosphorylated tau protein in neurons
neuronal degeneration in midbrain and frontal subcortical white matter
neurofiibrillary inclusions in neurons and glia
Dystonia
Sustained and/or phasic contraction of muscle causing abnormal posture or repetitive movements
Sensory trick to fix problem
Co-contraction of agonist-antagonist muscle
Idiopathic:
Childhood onset
Wilson’s disease
Autosomal recessive hereditary disease confused with Parkinson’s (Chromosome 13)
Onset: adolescence
Deficient copper excretion-copper transporter gene defect
High serum/urine copper, low ceruloplasmin
Copper deposition in:
Liver-hepatic failure
Basal ganglia-Akinetic rigid wing beating tremor
Dystonia, chorea
Psychiatric problems mimics schizophrenia
Descemets membrane:Kayser fleischer ring in eye
Some extent symptoms are reversible
Gross Pathology: atrophy and discoloration of putamen and globus pallidus
Microscopic pathology: neuronal loss and gliosis in putamen
Hemiballismus
Rapid large amplitude, unilateral, proximal flinging movements
Sudden onset stroke in contralateral subthalamic nucleus
Tics Tourette’s syndrome
Vocal and motor tics Affects males more before 20 yoa Autosomal dominant with low penetrate Associated with OCD Treatment: alpha-1 adrenergic receptor agonists, dopamine antagonists, Botox injections, or no treatment
Huntingtons disease
Causes chorea (bursts of movement)
Occurs between 30-50
Lesions in: caudate, putamen, globus pallidus, and cerebral cortex
Pathogenesis: deficiency of GABA, ACh, enkephalin and substance P
Trinucleotide CAG expansion-autosomal dominant
higher repeats more common in paternal lineage and earlier onset (happens during spermatogenesis)
Polyglutamine accumulation and inclusions leads to pathological interactions with other proteins
increased histone deacetylation silences neurons needed for survival preventing gene transcription of genes coding neutrophic factors
More severe symptoms with successive generations
Chorea, psychiatric (depression, dementia, psychosis, aggression) and cerebellar features, athetosis (snakelike movements of fingers)
Atrophy of caudate nucleus-box-car ventricles-dilation of frontal honrs of lateral ventricles
Loss of neurons in caudate, putamen, globus pallidus and cerebral cortex
Suicide is common form of death
Syringomyelia
Cavity in the cervical spinal cord
Occurs at cervical levels (C8-T1)
Loss of pain and temp symmetrically in the hands and wasting of hand muscles
Encroachment of the cystic cavity in the cord on the anterior commisure
Upper extremity weakness and hyporeflexia
Lower extremity weakness and hypereflexia
Kyphoscolioisis
Can affect lateral corticospinal tract
Associated with chiari type I malformation: cerebellar ectopia
Spinocerebellar ataxia
Mostly autosomal dominant
slowly progressive incoordination of gait associated with poor coordination of hands, speech and eye movements. Atrophy of the cerebellum.
Lesions in spinal cord and peripheral nerves
Caused by expansions of CAG repeats which encode polyglutamine regions in proteins
Intracerebral hemorrhage
Etiolgies: HITAAAA
clinical presentation: smooth progressive from mins to hours
Altered level of consciousness
High attenuation on CT
Putaminal-most common site, contralateral hemiparesis
Thalamic->3.3 cm usually fatal, contralateral hemisensory
Cerebral infarct
Etiology: atherosclerosis, stenosis, embolus
Third leading cause of death after non cerebral cardiovascular disease and cancer
Imaging: vascular distribution looks hypodense on CT, can be associated with hemorrhage
Findings on cat may not be present within 24 hrs
Earlier detection on diffusion weighted MRI
Ct rules out thrombolysis
MRI with perfusion assesses for irreversibly injured tissue
Cerebrovascular AVM
Abnormal communicating vessels-congenital
Present initially with hemorrhage
Combo of CT, MRI, MRA and conventional contrast angiography
Malignant hyperthermia
Heritable disorder
Caused by combination of volatile anesthetics and NMJ blocking agents
Can lead to death
Symptoms: tachycardia, hypertension, severe muscle rigidity, hyperthermia, hyperkalemia, acid base imbalance
Dantrolene treats the increase in free Ca2+ concentration
Giant cell arteritis
Abrupt vision loss, headache, jaw pain,
Diagnosis: Erythrocyte sedimentation rate elevated
Looking for giant cells in temporal artery biopsy
Opthalmic emergency
Treatment: long term steroids
Acute hyperammonemia
Due to liver dysfunction elevated serum ammonia levels
Ammonia crosses BBB and is neurotoxic
Leads promptly to neurological symptoms, coma and them death
Major contributor to hepatic encephalopathy
Von hippel lindau disease
Cavernous hemangiomas in skin,mucosa, organs; bilateral renal cell carcinomas, hemangioblastomas in retina,brain stem, cerebellum, and pheochrmocytoma
Autosomal dominant
Mutated vhl tumor suppressor gene on chromosome 3
Constitutive expression of HIf
Vacuolated cells
Meningocele
Meneinges but not the spinal cord herniate through spinal canal defect
Normal AFP
Associaed with Valproate which inhibits folate absorption
Thalamic Syndrome
Complete loss of contralateral sensory
Severe proprioception defects leads to unsteady gait and falls
Incomplete lesions or partial resolution leads to painful stimuli on affected side
Cerebellum lateral lesions
Voluntary movement of extremetities
Propensity to fall toward injured side (ipsilateral side)
Cerebellum medial lesions
lesions involving vermis, fastigial nuclei and/or the flocculonodular result in truncal ataxia, nystagmus and head tilting
May have wide based gait and deficits in truncal coordination
Bilateral motor deficits affecing axial and proximal limb musculature
Subacute cerebellar degeneration
Paraneoplastic (autoimmune)
Associated with lung, breast, ovarian, and uterine cancer
Progressive worsening dizziness, lung and truncal ataxia, dysarthia, and visual disturbances
Immune response to tumor cross reacts with purkinje neuron Ags leading to degeneration of cerebellum
Anti-yo, anti P/Q, anti Hu Abs in serum
Athetosis
Slow writhing movements especially in fingers
Lesion in basal ganglia
Myoclonus
Sudden brief uncontrolled muscle contraction
Jerks, hiccups,
Common in renal and liver failure
Dystonia
Cervical=spasmotic torticollis
Sustained involuntary muscle contractions sometimes painful
Can be suppressed by opposing action
May be basal ganglia lesion
Ex: writers cramp, sustained eyelid twitch
Essential tremor (postural tremor)
Action tremor exacerbated by holding posture/limb position
Genetic predisposition (AD) Patients often self medicate with alcohol which decreases tremor amplitude
Treatment: beta blockers, primiodone
resting tremor
Uncontrolled movement of distal appendages (most noticeably hands)
Tremor alleviated by intentional movement
Seen in parkinson’s disease
Intention Tremor
Slow, zig zag motion when pointing/extending toward a target
Cerebellar dysfunction
Chorea
Sudden, jerky purposeless movements
Lesion in basal ganglia
Spina bifida occulta
Failure of bony spiral canal to close but no structural herniation
usually at lower vertebral levels
Dura still intact
associated with dandy walker
Associated with tuft of hair or skin dimple at level of bony defect
Neural Tube Defects Overall Characteristics
Neuropores fail to fuse in the fourth week
Associated with low folic acid intake
Elevated a-fetoprotein in aminiotic fluid and maternal serum
increased Acetylcholinesterase in amniotic fluid
Anterior: encephalopathy, ancephaly
Posterior=spina bifida, menigocele, menigomyelocele, rachischis (failure of vertebral column to fuse)
Transcortical motor vs transcortical Sensory vs. mixed aphasia
Motor: nonfluent aphasia with good comprehension and repetition (Brocas cant repeat)
Sensory: poor comprehension with fluent speech and repetition
Mixed: nonfluent speech, poor comprehension, good repetition
Hypoxic ischemic encephalopathy
Profound hypotension affects watershed areas-appear as bilateral wedge shaped bands of necrosis over cerebral convexity lateral to interhemispheric fissure
Interruption for 10 seconds leads to syncope
4-5 mins leads to permanent damage
Gray matter affected first
Hippocampus also affected
Upper/leg upper arm weakness, defects in higher-order visual processing
Berry Aneurysm
Abnormal dilation of artery due to weakening of vessel wall
Occurs at bifurcation of circle of willis-Anterior communication and ACA are most common
Rupture leads to subarachnoid hemorrhage (worst headache of my life) or hemorrhagic stroke
can also cause bitemporal hemianopia with compression of optic chiasm
Associated with ADPKD, Ehlers Danlos Syndrome, an Marfan syndrome
risk factors: advanced age, hypertension, smoking, increased in blacks
Blood can be found in CNS
Charcot bouchard microaneurysm
Associated with chronic hypertension
Affects small vessels-basal ganglia and thalamus
Post stroke pain syndrome
Neuropathic pain due to thalamic lesions
Initial sensation of numbness and tingling follwed in weeks to months by allodynia (oridinarily painless stimuli cause pain) and dysaethesia (abnormal sense of touch)
occurs in 10% of stroke patients
Cerbral Amyloid angiopathy
RECURRENT lobar hemorrhages in elderly
B-amyloid deposited in arterial wall leading to weakening of wall and predisposition to rupture
Recurrent hemorrhagic stroke most common presentation-less severe
located in cerebral hemispheres
Intraventricular hemorrhage
Complication of premturity
Can lead to neurodevelopment impairment
infants born before 32 weeks or BW
Conducation aphasia
Poor repetition but fluent speech, intact comprehension
(can’t repeat phrases no ifs and or buts)
Damage to left superior temporal lobe and/or left supramarginal gyrus
Brocas Aphasia
Nonfluent aphasia with intact comprehension
Broca area-inferior frontal gyrus of frontal lobe
Repetition impaired
Right hemiparesis
MCA impaired
Wernicke’s aphasia
Fluent aphasia with impaired comprehension and repitition
Wernicke area-superior temporal gyrus of temporal lobe
Words make no sense
Right superior quadrant field defect
MCA impaired
Global Aphasia
Nonfluent aphasia with impaired comprehension
Both Broca and Wernicke areas affected
Subdural Hematoma
Rupture of bridging veins
Slow venous bleeding-less presssure hematoma develops over time
Seen in elderly, alcoholics, blunt trauma, shaken baby syndrome (brain atrophy, shaking whiplash)
Babies will also have bilateral retinal hemorrhages
Crescent shaped hemorrhage that crosses suture lins
Midline shift
Cannot cross falx, tentorium
Between dura and arachnoid
gradual onset of headache and confusion
Transient ischemic attack
Brief reversible episode of focal neruologic dysfunction lasting
Brown Sequard syndrome
Hemisection of spinal cord
Ipsilateral UMN signs below the level of the lesion (corticospinal tract damage)
Ipsilateral loss of tactile, vibration, proprioception 1-2 levels below the level of lesion (dorsal column damage)
Contralateral pain and temperature loss below the level of lesion (spinothalamic tract damage)
Ipsilateral loss of all sensation at the level of the lesion
Ipsilateral LMN lesion at level of lesion
Above T1 may present with Horner Syndrome
Horner Syndrome
Sympathetic dysfunction
Ptosis (superior tarsal muscle)
Anihidrosis: absence of sweating and increased flushing on affected side of face
Miosis: pupil constriction
Hypothalamus to lateral horn (1st synapse)
lateral horn to superior cervical ganglion (2nd synapse)
Then to smooth muscle of eyelid, sweat glands to forehead/face, pupillary dilator muscle
Associated with spinal cord lesions above T1-pancoast tumor, brown sequard, late stage syringomyelia
Conus Medullaris Syndrome
L2=Conus medullaris
Caused by disk herniation, tumors and fractures
Flaccid paralysis of bladder and rectum, impotence and saddle anesthesia
Cavernous Sinus Syndrome
Mass effect, fistula or thrombosis
Ophthalmoplegia (paralysis of extraocular muscles) and decreased corneal and maxillary sensation with normal visual acuity
CN VI commonly affected
Conductive Hearing Loss
Obstruction of external sound vibrations
Rinne test: Abnormal-Bone greater than air
Weber test: Louder sound in affected ear
Causes: cerumen impaction, cholesteatoma, otosclerosis, external or middle ear tumors, tympanic membrane rupture, severe otitis media
Sensorineural hearing loss
Inner ear, cochlea or auditory nerve damage
Rinne test: normal air greater than bone
Weber: louder sound in unaffected ear
Causes: Meinere’s disease, acoustic neuroma, presbyscusis, ototoxic drugs
Noise induced hearing loss
Damage to sterocilliated cells in organ of Corti
Prolonged exposure to noises greater than 85dB
Acoustic reflex dampens effects of prolonged noise because the stapedius and tensor tympani muscles contract lessening ossicles response to sound
Loss of high frequency sound first
Sudden exposure to loud noises can cause tympanic membrane rupture
Hyperacusis
CN VII innervates stapedius muscle via stapedius nerve
paralysis of stapedius causes the stapes to ossicillate more widely-hyperacusis
patients present with increased sensitivity to everyday sounds and will withdrawal socially
treatment: retaining therapy using broadband noise (white noise)
CN V3 innervates tensor tympani (sphenoid bone to malleus) which contracts tympanic membrane dampening sound
Hyperopia
Refractive error that improves with glasses
Hyperopia: eye too short for refractive power of cornea and lens light is focused behind the eye
Farsightedness: distant objects seen clearly
(too short and hyper so he fell FAR behind)
Myopia
Refractive error corrected with glasses
Nearsightedness: can see near objects
Eye too long for refractive power of cornea and lens
Light focused in front of retina
(My you’re long! You shouldn’t be so NEAR the front
Astigmatism
Abnromal curvature of cornea resulting in different refractive power at different axes
Presbyopia
Decrease in focusing ability during accommodation due to sclerosis and decreased elasticity
Central Retinal artery occlusion
Acute, painless, monocular vision loss
Retina cloudy with attenuated vessels and cherry-red spot at fovea
(macula supplied by choroid artery of MCA)
Vision loss includes entire visual field and is permanent
Most common cause: embolism
Open Angle Glaucoma
Optic disc atrophy with characteristic cupping, with increased Intraocular pressure and poregressive visual field loss
Chronic glaucoma
Gradual increase in fluid in anterior and posterior chambers
Canal of schlemm is still open but drainage is slow
Associated with increased age, African American race, family history
Painless
Primary: unclear cause
Secondary: Blocked trabecular meshwork from WBCs (Uveitis),, RBCs (vitreous hemorrhage), retinal elements (retinal detachment)
Closed Angle Glaucoma
Acute
Optic disc atrophy with charaacteristic cupping, increased intraocular pressure and progressive peripheral visual field loss
increase pressure in just posterior chamber
Primary: enlargement or forward movement of lens against iris obstruction of aqueous flow through pupil-fluid builds up behind iris, pushing peripheral iris against cornea and impeding flow through trabecular meshwork
Painful, sudden vision loss, halos around light, rock-hard eye, frontal headache-do not give epihephrine due to mydriasis
Secondary: hypoxia from retinal disease (diabetes, or vein occlusion) induces vasoprliferation in iris that contracts angle
Precipitated by anti-cholinergic medicatiotns
Retinal Detachment
Separation of nerosensory layer of retina (photorecpetor layer with rods and cones) from outermost pigmented epithelium (normally shields excess light, supports retina) leads to degeneration of photoreceptors and vision loss
May be secondary to retinal breaks, diabetic traction, inflammatory effusions
Breaks more common in patients with high myopia and are often preceded by posterior vitreous detachment (flashes and floaters) and eventual monocular loss of vision
surgical emergency
Macular degeneration
Degeneration of macula (central area of retina)
Macula is densely packed with cones and has increased visual acuity, no blood vessels
Projects to single bipolar cell
Causes distortion and eventual loss of central vision (scotomas)
(visual defect surrounded by an unaffected eye)
Dry: (more common) deposition of yellowish fatty tissue beneath Bruch membrane and retinal pigment epithelium with gradual loss in vision (impaired driving and reading)
Due to chronic oxidative damage to retinal epithelium and choriocapillaries
Prevent progression to “wet” with mulitvitamin (zinc) and antioxidants (smoking cessation)
wet: rapid loss of vision due to secondary bleeding of choroidal neovascularization
Due to hypoxia
Treat with anti-VEGF (Ranibizumab and pryaptanib) or laser
