Neuropathology 2

Question 1

What is chorea?

Diseases associated?

Answer 1

Involuntary, jerky, purposeless movements that arise from basal ganglia lesions
Inherited disorders: HD, Neuroacanthocytosis, Wilson’s disease
Infectious - strep infection - rheumatic fever
Drug induced chorea - neuroleptics (phenothiazines, haloperidol), phenytoin, oral contraceptives in women with SLE, L-dopa and DA agonists, cocaine

Question 2

What is athetosis

Answer 2

Not fixed, snake like writhing, especially of the fingers

Basal ganglia lesions, antipsychotics e.g. haloperidol

Question 3

What is hemiballismus? Causes

Treatments?

Answer 3

Sudden, uncontrolled flailing of one limb due to lesions in contralateral STN (subthalamic nucleus)
Interrupts inhibitory indirect pathway
Treatments: Haloperidol, phenothiazine

Question 4

Broca’s aphasia?

Answer 4

Motor/nonfluent/expressive aphasia - occurs in inferior frontal gyrus, brodmann 44, patients are nonfluent, with good comprehension, impaired repetition, speak in short monosyllabic words, aware of deficit, frustrated
Assoc. contralateral arm and face weakness
Lesions in superior left MCA

Question 5

Wernicke’s aphasia?

Answer 5

Superior temporal gyrus, brodmann 22,
Sensory/fluent/auditory aphasia - with impaired comprehension, neologisms, paraphasic errors, and impaired repetition
Speech is fluent but nosensicl ‘word salad”
Unaware of deficit
Assoc. visual deficit, contralateral RU quadrantanopia, due to meyer’s loop in temporal lobe, alexia

Question 6

Conduction aphasia?

Answer 6

Lesions to arcuate fasciculus that connects the two language centers, poor repetition with intact comprehension and fluent speech
Cannot name objects

Question 7

Global aphasia?

Answer 7

Both speech and comprehension affected, large perisylvian or separate frontal and temporal lesions
Assoc. right hemiplegia, right hemianesthesia, and homonymous hemianopia

Question 8

Degenerative diseases
Classic symptoms with cerebrum lesions?
CST? Basal ganglia? cerebellum?

Answer 8

CST - motor deficits
Cerebrum - personality changes, memory loss, seizures cognitive dysfunction
Basal ganglia -movements disorders
Spinocerebellar/cerebellum lesions - manifest in ataxia

Question 9

Name 3 diseases associated with motor neuron lesions?

Answer 9

1. ALS
2. Werdnig-Hoffman syndrome (floppy baby)
3. Poliomyelitis

Question 10

What is ALS? Features?

Answer 10

• Amyotrophic Lateral Sclerosis - associated with UMN and LMN signs sparing sensation, 40-60 years age of onset, assoc. chr. 21, SOD1 gene
• UMN signs - spasticity, +Babinski, hyperreflexia
• LMN signs - thenar atrophy, muscle weakness, denervation atrophy
• Rapidly fatal due to resp. failure - use Riluzole to delay ventilator/tracheostomy use

Question 11

What is Werdnig-Hoffman disease?

Features? Pathology?

Answer 11

• Autosomal “recessive inheritance that manifests at birth as “floppy baby syndrome”
• Tongue fasciculations, LMN disease
• Degeneration of anterior horn cells
• no UMN, or CST degeneration
• congenital variant of ALS with only LMN signs
• Defect in gene turns of peri-natal apoptosis
• Median age of death - 7 years

Question 12

Poliomyelitis? features? causes? treatment?

Answer 12

-Follows infection (fecal-oral) with poliovirus
Replicates in oropharynx and small intestine before hematologic spread to CNS, presents with LMN signs
-CSF with lymphocytic pleocytosis, slight increase in protein
-virus recovered from stool or throat
-Degeneration of anterior horn cells
-Treatment: hospitalize with strict bed rest to reduce paralysis, ventilation to treat resp. muscle weakness

Question 13

Alzheimer’s disease? features? presentation?

Answer 13

• Slow progressive mental deterioration with loss of short term memory, anosmia, language difficulties and planning skills, decline in executive function
• Spares primary sensory and motor areas
• Generalized cerebral atrophy –> widened sulci, hydrocephalus ex vacuo
• Most common dementia in elderly

Question 14

Alzheimer’s disease? Inheritance?

Answer 14

• Familial form (10%) associated with early onset (before 40 yrs)
• Genetic causes - presenilin 1 and 2 on chr. 1 and 14 - causing hyperphosphorylated tau and neurofibrilliary tangles, APOE4 allele on chr. 19, p-APP on chr. 21
• p-APP increases amount of APP, trisomy 21 is assoc. with early -onset AD (30-40 yrs)

Question 15

Alzheimer’s disease? Pathology?

Answer 15

• senile plaques (Beta-amyloid surrounded by dystrophic neuritis in extracellular space
• neurofibrillary tangles (intracellular abnormal tau protein, silver stain positive)
• Beta-amyloid is toxic when deposited on neurons and cerebral blood vessels (cerebral amyloid angiopathy) causing intracranial hemorrhage
• decreased ACh due to loss of cholinergic nuclei in forebrain nucleus basalis of Meynert

Question 16

Alzheimer’s disease? Treatment?

Answer 16

1. Donezepil - ACE inhibitors that cross BBB
2. NMDA receptor antagonists - memantine reduce glutamate -mediated excitotoxicity
   - Not disease modifying

Question 17

Name 3 diseases assoc. with cerebral cortex lesions?

Answer 17

1. Alzheimer’s Disease
2. Pick’s disease
3. Vascular dementia (multi-infarct)

Question 18

Pick’s disease? features? pathology? treatment?

Answer 18

• First sign is personality changes (disinhibition, dementia, impaired judgement, with aphasia)
• Frontal -temporal atrophy with gliosis, loss of white matter
• Has aspects of AD but with early onset (

Question 19

Multi-infarct (vascular dementia) -features?

Answer 19

-2nd common cause of dementia
-Progressive, stepwise decline in functioning (instead of gradual cause in AD)
secondary to atherosclerosis
-Treatment underlining vascular cause, stroke prevention

Question 20

Name 4 diseases associated with Basal ganglia lesions?

Answer 20

1. Huntington’s disease
2. Parkinson disease
3. Wilson’s disease
4. Dementia with Lewy bodies (DLB)

Question 21

Huntington’s Disease: Features?

Answer 21

-Autosomal dominant with complete
penetrance 
-Progressive devo. of athetoid chorea in all
four limbs (writhing), dementia, and
emotional disturbances. Onset at
35-45 years with anticipation.
-Atrophy of the caudate (head)
and putamen-- lateral
ventricles enlarged ("bat-wing" frontal horns).
-Hydrocephalus ex vacuo
-spared memory

Question 22

Huntington’s disease: Pathology?

Answer 22

-Atrophy of striatum –> loss of
medium spiny (GABAergic) neurons
-Expansion of CAG triplet repeats
(polyglutamine) in huntingtin
gene on chr. 4 –>aggregation of mutant huntingtin – toxic
-Expansion of CAG repeats (anticipation).
Caudate loses ACh and GABA.

Question 23

Huntington’s disease: Treatment?

Answer 23

-Symptomatic treatment with
haloperidol effective in
suppressing movement disorder
-Incurable, progressive decline, death in 15-20yrs, increase rates of suicide
-allele more unstable during spermatogenesis

Question 24

Parkinson disease: Clinical features?

Answer 24

Tremors
Rigidity
Akinesia/bradykinesia
Postural instability
Shuffling gait
Expressionless face, flat affect
Dementia (late)
-en bloc turning
-small handwriting

Question 25

Parkinson disease: Pathology

Answer 25

``` -Degenerative disorder of CNS associated with Lewy bodies (composed of α-synuclein—intracellular eosinophilic inclusions and loss of dopaminergic neurons (i.e., depigmentation) of substantia nigra pars compacta. ```

Question 26

Parkinson Disease: Treatment

Answer 26

BALSA: Bromocriptine - DA agonist Amantadine -increase DA release, decrease DA reuptake Levodopa (with carbidopa) —carbidopa blocks peripheral conversion of l-DOPA to dopamine by inhibiting DOPA decarboxylase. Selegiline (and COMT inhibitors) -blocks conversion of dopamine into 3-MT by selectively inhibiting MAO-B. Antimuscarinics - Benztropine, improves tremor and rigidity

Question 27

Wilson's disease: pathology?

Answer 27

-(hepatolenticular degeneration) results from autosomal recessive mutations in a membrane-bound copper transporter that overwhelms copper capacity because of an inability to excrete copper into bile. -Copper is deposited in the putamen and globus pallidus, liver, eyes -liver biopsy and copper quantification

Question 28

Wilson's disease: Features

Answer 28

``` Characterized by: -Decreased -Ceruloplasmin -Cirrhosis -Corneal deposits (Kayser-Fleischer rings), -Copper accumulation -Carcinoma (hepatocellular) -Hemolytic anemia -Basal ganglia degeneration (parkinsonian symptoms) -Asterixis -Dementia, Dyskinesia, Dysarthria “Copper is Hella BAD.” ```

Question 29

Wilson's disease: tx?

Answer 29

``` -Zinc, penicillamine (copper chelator) + pyridoxine to prevent anemia effective at preventing progression of neurologic symptoms; low-copper diet. -Liver transplant ```

Question 30

Dementia with Lewy bodies: features? tx?

Answer 30

-Initially dementia and visual hallucinations (“haLewycinations”) followed by parkinsonian features. -α-synuclein defect (Lewy bodies, primarily cortical) -substantia nigra, limbic system, NBM -Selegiline and other MAO inhibitors

Question 31

Progressive Supranuclear Palsy: features?

Answer 31

-widespread neuronal loss and subcortical gliosis that notably spares the cerebral and cerebellar cortices -Presents in 60s, difficulty in vertical movement of gaze, pseudobulbar palsy (dysarthria, dysphagia, hyperactive jaw jerk and gag reflexes, and uncontrollable laughing or crying unrelated to emotional state) -axial dystonia with repeated falls, and bradykinesia without resting tremor ("atypical Parkinsonism") . -Memory and intellect intac -prominent neurofibrilliary tangles

Question 32

Friedreich ataxia? features?

Answer 32

-Autosomal recessive trinucleotide repeat disease (GAA) involving frataxin gene, with onset of symptoms in the first decade of life. -Loss of proprioception, decreased deep tendon reflexes, positive Babinski sign.

Question 33

Friedreich ataxia? associations?

Answer 33

-Associated with myocarditis, hypertrophic cardiomyopathy, scoliosis, hearing/vision impairment, and high plantar arches (pes cavus).

Question 34

Friedreich ataxia? pathology?

Answer 34

- "Atrophy of spinal cord," diffuse damage to dorsal columns, spinocerebellar tracts, and lateral corticospinal tracts. - poor prognosis, no definitive treatment

Question 35

Multiple sclerosis: presentation?

Answer 35

-Autoimmune inflammation and demyelination of CNS (brain and spinal cord). -Patients can present with optic neuritis (sudden loss of vision resulting in Marcus Gunn pupils), INO, hemiparesis, hemisensory symptoms, bladder/ bowel incontinence. -Relapsing and remitting course. -Most often affects women in their 20s and 30s; more common in whites living further from equator.

Question 36

MS: Classic triad? tx?

Answer 36

``` Charcot classic triad of MS is a SIN: ƒ ---> Scanning speech ƒ ---> Intention tremor (also Incontinence and Internuclear ophthalmoplegia) ƒ ---> Nystagmus ``` Tx: Slow progression with disease-modifying therapies (e.g., β-interferon, natalizumab). -Treat acute flares with IV steroids.

Question 37

MS: Findings

Answer 37

-Increased protein (IgG) in CSF. -Oligoclonal bands are diagnostic. -MRI is gold standard. Periventricular plaques (areas of oligodendrocyte loss and reactive gliosis) with destruction of axons. -Multiple white matter lesions separated in space and time.

Question 38

Acute inflammatory demyelinating polyradiculopathy (AIDP): features?

Answer 38

-Most common subtype of Guillain-Barré syndrome. Autoimmune condition that destroys Schwann cells --> inflammation and demyelination of peripheral nerves and motor fibers. -Results in symmetric ascending muscle weakness/paralysis beginning in lower extremities.

Question 39

Acute inflammatory demyelinating polyradiculopathy (AIDP): findings? assoc.? tx?

Answer 39

-Findings: increased CSF protein with normal cell count (albuminocytologic dissociation). 􀁱 protein may cause papilledema -Associated with infections (e.g., C. jejuni, viral) --> autoimmune attack of PNS myelin due to molecular mimicry, inoculations, and stress, but no definitive link to pathogens. -Respiratory support is critical until recovery. -Additional treatment: plasmapheresis, IV immunoglobulins.

Question 40

------ viruses causes these ------- demyelinating diseases

Answer 40

``` - Viral infection of oligodendrocytes is the key feature of subacute sclerosing panencephalitis (measles paramyxovirus) and progressive multifocal leukoencephalopathy (JC virus). ```

Question 41

--- (disease) affects only white matter, --- affects both white and gray matter, --- affects only gray matter

Answer 41

``` - Only white matter is affected in PML (Progressive Multifocal Leukoencephalopathy) -subacute sclerosing panencephalitis, affects both white and gray matter -rabies, affects only gray matter. ```