Board Neurology Review Flashcards
1
Q
Type 1, 2, 3, 5 and 7 Glycogen storage disease names
A
Type 1 - Von Gierke’s
Type 2 - Pompes
Type 3 - Cori’s
Type 5 - McArdle
Type 7 - Tauri’s
2
Q
Inheritance pattern of all the glycogen storage diseases
A
autosomal recessive
3
Q
enzyme deficiency in von gierke disease
A
glucose-6-phosphatase deficiency
4
Q
enzyme deficiency in Pompe’s disease
A
acid maltase (alpha-galactosidase)
5
Q
enzyme deficiency in Cori’s disease
A
debranching enzyme amylo-1,6- glucosidase
6
Q
enzyme deficiency in McArdle’s disease
A
myophosphorylase
7
Q
enzyme deficiency in Tauri disease
A
phosphofructokinase
8
Q
Hurler Syndrome
A
- MPS1 -autosomal recessive
- enzyme: a-L-iduronidase
- elevated urine dermatan and heparin sulfate
- mental retardation, gargoyle face, thick meninges, CORNEAL CLOUDING, retinopathy, cardiac disease, deafness
- usually fatal by 10 years from cardiac or respiratory complications
- ZEBRA BODIES
9
Q
Hunter Syndrome
A
- MPS2 -X linked recessive
- enzyme: iduronate-2-sulfatase
- dwarfism, HSM, coarse facial features, deafness, hydrocephalus
- minimal mental retardation, slower disease
- the severe variant can cause death 15 yoa
- INCREASED URINARY EXCRETION OF DERMATAN SULFATE
- no corneal clouding -pebbled skin over the scapula
10
Q
Scheie syndrome
A
- milder form of Hurler syndrome
- autosomal recessive
- enzyme: a-L-iduronidase
- may like normal lifespans
- no mental retardation
- spinal cord compression and corneal opacities can occur
- increased urinary dermatan and heparin sulfate -zebra bodies
11
Q
Sanfilippo Syndrome
A
- MPS3
- autosomal recessive
- increased urinary excretion of heparin sulfate
- enzyme: heparin sulfatase
- mental retardation, ataxia, hirsuitism, seizures, dementia, and progressive quadriparesis
12
Q
Morquio’s Syndrome
A
- MPS4
- autosomal recessive
- enzyme: B-galactosidase or galactose-6-sulfatase (severe)
- dwarfism, joint laxity, HSM, deafness, cardiac disease, respiratory disease
- AA subluxation -> cervical cord compression
- increased urinary excretion of keratan sulfate
- death from respiratory or cardiac failure usually occurs in 3rd decade
13
Q
Maroteaux-Lamy syndrome
A
- MPS 6
- autosomal recessive
- enzyme: arylsulfatase B
- urinary dermatan sulfate
- cervical myelopathy, HSM, no mental retardation
14
Q
sly’s Syndrome
A
- MPS7
- autosomal recessive
- enzyme: B-glucouronidase
- urinary heparan, dermatan and chondroitin sulfate
- mental retardation, corneal clouding, HSM, bony changes
15
Q
Enzyme deficiency in Krabbe disease
A
Galactocerebrosidase B-galactosidase
16
Q
krabbe disease
A
- AR
- enzyme: Galactocerebrosidase
- accumulation: psychocine -> primarily affects oligodendrocytes
- histology: globoid macrophages
- symptom onset 3-6months of age
- hypertonicity, hyper-reflexia followed by progresive flaccid paralysis and loss of DTRs, dysphagia, seizures and death by 2-3 years of age
17
Q
Alexander disease
A
- sporadic inheritance
- infants in first year of life with macrocephaly, spasticity, seizures, gradual loss of developmental milestones
- numerous Rosenthal fibers
- initially affects frontal lobe white matter before progressing posteriorly
18
Q
Metachromatic Leukodystrophy
A
- autosomal recessive
- enzyme: arylsulfatase A deficiency
- most common leukodystrophy
- abnormal accumulation of sulfatide and affects both peripheral and central myelin
- flaccid paralysis, decreased DTRs, slowed NCV, optic atrophy, pseudobulbar palsy
- SPARES SUBCORTICAL U FIBERS
- hirsch-peiffer reaction -> tissue turns brown with acidic cresyl violet
- PAS + macrophages
19
Q
Adrenoleukodystrophy
A
- X-linked
- defective peroxismal very long chain fatty acid B-oxidation
- accumulation: very long chain fatty acids
- present between 5 and 8 yoa
- bronze skin, dementia, behavior changes, optic atrophy, neuropathy, adrenal insufficiency, mental retardation
- SPARES U FIBERS
- PARIETO-OCCIPITAL CAVITATION
20
Q
Pelizaeus-Merzbacher Disease
A
- X linked Recessive
- deficient or abnormal myelin proteolipid protein
- presents in infancy with spasticity, ataxia, optic atrophy, seizures, rotatary nystagmus, delayed development
21
Q
Canavan Disease
A
- AR
- enzyme: aspartoacylase (amino-acidopathy)
- presents b/w 2 and 4 months of ae
- hypotonia, optic atrophy, developmental delay, macrocephaly
- markedly enlarged mitochondria
- INVOLVES SUBCORTICAL U FIBERS
- INCREASED NAA ON MRS
- predilection for Ashkenazi Jews
22
Q
Gaucher Disease
A
- AR
- enzyme: glucocerebrosidase deficiencey
- accumulation: glucocerebrosides
- 4 types
- infantile form -> cherry red macula, HSM, seizures, early death
- thrombocytopenia, anemia
- chronic non-neuonopathic form -> visceral storage in spleen, kidneys, heart, liver
- WRINKLED TISSUE PAPER CELLS
23
Q
Tay-Sachs Disease
A
- AR
- deficiency in Hexoaminidase A
- accumulation of Gm2 gangliosides
- presents between 4-6 months of age
- hyper-reflexia, seizures, hypotonia, cherry red macula, blindess, myoclonic jerks, MACROCEPHALY
- death by 3-5; ashkenazi jews
24
Q
Sandhoffs disease
A
- AR
- deficiency in Hexoaminidase A&B
- similar to tay sachs; cherry red maculo, HSM
25
Q
Infantile GM2 Gangliosidosis
A
- AR
- deficiency B-galactosidase
- cherry red macula, HSM, BONY ABNORMALITIES, dysmorphic facial features, contractures
26
Q
Neimann Pick Disease
A
- AR
- deficiency in sphingomyelinase
- accumulation of sphingolipids
- FOAM Cells
- hypotonia, mental retardation, cherry red macula, HSM, usually die 4-5yrs
- ataxia, seizurs, supranuclear vertical gaze palsy
27
Q
Fabry Disease
A
- X linked recessive
- deficiency in Alpha-galactosidase A
- accumulation of ceramide trihexoside in skin, blood vessels, kidney, heart
- extremity pain or paraesthesias, telangiectasia, renal failure, cardiomyopathy, LARGE PURPLE MACULAR LESIONS
- CVA
- skin angiokeratomas
- AVN of femur
28
Q
Phenylketonuria
A
- AR
- deficiency in phenylalanine hydroxylase
- increased serum phenylalanine, increased urine phenyl pyruvic acid
- diagnosed in neonates with screening
- mental retardation, seizures, hyper-reflexia, fair-skinned, blue eyes
- MUSTY ODOR TO URINE
- tx - low phenylalanine diet to prevent mental retardation
29
Q
Maple Syrup Urine Disease
A
- AR
- defects in the metabolism of branched-chain amino acids
- hypertonia, seizures, opisthotonos, developmental delay, opthalamoplegia, SWEET-SMELLING ODOR
- tx -> diet low in branched-chain amino acids (isoleucine, leucine, valine) and thiamine supplementation
30
Q
Homocystinuria
A
- AR
- deficiency in cystathionine B-synthase
- increased serum and urine homocystine and methionine
- intimal thickening and fibrosis of blood vessels -> multiple strokes, dural sinus thrombosis
- mental retardation; tall, thin, lens dislocation
- Tx: B6, B12. decreased methionine, INCREASED CYSTEINE INTAKE
31
Q
Hartnup disease
A
- defect in transport of neutral amino acids in the small intestine and kidneys
- mental retardation, ataxia, PHOTOSENSTIVE DERMATITIS (resembles pellagra), renal aminoaciduria
- Tx: niacin supplements and high protein diet
32
Q
Lesch-Nyhan Syndrome
A
- X linked recessive
- deficiency in hypoxanthane-guanine phosphoribosyltransferase
- increased levels of uric acid 2/2 to increased purine metabolism, and urate deposition can result in nephropathy and gout
- mental retardation, choreoathetosis, spasticity, self-mutilation and usually die from renal failure in the 2nd or 3rd decade of life
33
Q
Glucose transporter protein syndrome
A
- deficiency in glucose transporter 1-protein
- GLUT1 is responsible for the facilitated diffusion of glucose across the BBB
- decreased CSF glucose levels (hypoglycorrhachia), seizures, developmental delay, microcephaly, ataxia, hypotonia
- TX = ketogenic diet, thioctic acid allows for seizure control
34
Q
Zellewenger Syndrome
A
AKA cerebrohepatorenal syndrome
- AR
- perioxismal disorder that results in abnormalities of very-long chain fatty acids, bile acids, plasmalogen, and phyantic acid metabolism
- hypotonia, seizures, optic atophy, pigmentary retinopathy, cirrhosis of the liver, chacteristic facies
- fatal within a few months after birth frin cardiac issues
35
Q
Wilson Disease
A
AKA Hepatolenticular degeneration
- AR (chromosome 13)
- deficiency of copper-transporting ATPase in lever and kidneys
- biliary excretion of copper is decreased and formation of ceruloplasmin is impaired
- decreased serum ceruloplasmin, increased serum copper, increased urine copper levels
- cirrhosis, dysarthria, rigidity, chorea, tremor, ataxia, seizures, kayer-flesher rings (copper deposition in Descemet Membrane)
- MRI -> increased signal in basal ganglia on T1 or T2; caudate and putamen atrophy
- TX -> penicillamine or ammonium tetrathiomolybdate and zinc
36
Q
Acute intermittent porphyria
A
- abnormality in heme metabolism
- autosomal dominant
- defective porphobilinogen deaminase
- INCREASED URINARY PORPHOBILINOGEN AND d-ALA; urine turns dark as it oxidizes
- acute attacks -> abdominal pain, n/v/d, myalgia, seizures, delirium, psychosis, peripheral neuropathy
- TX -> propranolol, hematin, and diazepam for seizure control
37
Q
what drugs can cause an acute attack of AIP?
A
barbituates, benzos, sulfonomides, hormone therapy, low carb intake
38
Q
Hallervorden-Spatz Disease
A
AKA Panthothenate Kinase Associated Denegeration
- AR
- excessive iron deposition in the brain
- parkinsonism, dystonia, dementia, frozen facial expressions
- MRI -> decreased signal in GP (eye of the tiger) on T2
- Definitive dx at autopsy
- Tx -> phosphopanthothenate
39
Q
Levine-Critchley syndrome
A
AKA Neuroacanthocytosis
- progressive multisystem neurodegenerative disorder that usually presents in the 4th to 5th decades
- psychosis, dementia, tics, hyperkinetic movement disoders, peripheral neuropathy and acanthocytes
- MRI -> severe atrophy of the caudate and putamen
- autosomal dominant (chromosome 9)
- death 10-15 years after symptom onset
40
Q
Superficial siderosis
A
- results from chronic deposition of hemosiderin over the surfaces of the brain and spinal cord
- sensorineural hearing loss, cerebellar ataxia, myelopathy, dementia, anosmia
- hypointense rim along the surface of the brain and cerebellum on GRE and T2
- CSF -> acellular with prescence of xanthochromia
- tx -> find source of hemorrhage
41
Q
what type of inheritance pattern do mitochondrial disorders have?
A
maternal inheritance
42
Q
MELAS syndrome
A
Mitochondrial, myopathy, encephalopathy, lactic acidosis, and stroke like episodes
- generalized seizures, migrain headaches, emesis, dementia, strokes that result in hemiparesis, hemianopsia and cortical blindness
- Red-RAGGED FIBERS on muscle biopsy
43
Q
MERRF Syndrome
A
Myoclonic epilepsy wiht red-ragged fibers
- myoclonic epilepsy, mental deterioration, and proximal myopathy in children or adults
- slowly progressive
44
Q
Kearns-Sayre Syndrome
A
- mitochondrial disorder with triad:
1. progressive external opthalmoplegia
2. retinitis pigmentosa
3. cardiac conduction defects
4. onset before age 20 - increased CSF protein levels, increaesd serum pyruvate, spongy brain
- death by end of second decade usually
45
Q
Lebers hereditary optic neuropathy
A
- mitochondrial disorder
- progressive, PAINLESS, central vision loss and cardiac conduction abnormalities usually in the 3rd or 4th decades
46
Q
List mitochondrial disorders
A
- MELAS Syndrome
- MERRF syndrome
- Kearns Sayre Disease (not maternally inherited)
- Lebers Hereditary Optic neuropathy
47
Q
Enzyme deficiency thought to cause 20% of ALS
A
Cu/Zn superoxide dismutatase located on chromosome 21q
48
Q
Amyotrophic lateral sclerosis
A
- affects both upper and lower motor neurons
- most common motor neuron disease; worst prognosis
- most cares are sporadic; 20% of familial cases autosomal dominant Cu/Zn superoxide dismutase
- neuron degeneration occurs primarily in the anterior horns, corticospinal tracts, motor corte and the hypoglossal nucleus
- symptoms -> weakness, atrophy, fasciculations, spasticity, hyper-reflexia
- spastic and hyper-reflexic lower extremities, weak and atrophic upper extremities
- death 3-5 years from respiratory complications
49
Q
What is spared in ALS?
A
Extraocular muscles, SENSATION, sphincter function
50
Q
Kennedy’ Disease
A
AKA spinobulbar muscular atrophy
- trinucleotide repeat disorder (CAG)
- mutation -> androgen receptor gene on X chromosome
- X linked recessive, affects males
- LOWER MOTOR NEURON DEGENERATION ONLY
- dysarthria, dysphagia, limb weakness, hypo-reflexia, tongue fasciculations
- gynecomastia, infertility, PRIMARY SENSORY NEUROPATHIES
- slower progression
51
Q
Spinomuscular atrophy type 1
A
- infantile SMA (Werding-Hoffman disease)
- autosomal recessive, chromosome 5q
- marked hypotonia (floppy body), proximal muscle weakness
- death by 4-6 weeks due to respiratory failure
52
Q
spinomuscular atrophy type 2
A
- chronic infantile SMA
- begins between age 6 - 15 months
- AR
- contractures, scoliosis
- survive until 2-4 years of age
53
Q
spinomuscular atrophy type 3
A
AKA Kugelberg-Welander Disease
- AR
- chronic proximal SMA
- slowly progressive proximal limb weakness
54
Q
Adult-onset SMA
A
- autosomal dominant inheritance
- patient’s survive into 4th to 6th decades
55
Q
Friedreichs Ataxia
A
- autosomal recessive
- trinucleotide repeat disorder GAA
- frataxin gene mutation, chromosome 9q
- onset: 10-15 years, fatal by 5th to 6th decades
- Degeneration of the posterior columns, spinocerebellar tracts, corticospinal tracts, Clarke’s nucleus
- Symptoms -> ataxic gait, dysarthria, areflexia, lower limb weakness, loss of vibratory sense and proprioception
- cardiomyopathy; can lead to cerebellar and cortical ischemic changes
- peripheral neuropathy
- hammertoes, kyphoscoliosis, pes cavus
- no treatment
56
Q
Ataxia-telangiectasia
A
- AR; most common cause of progressive ataxia in infancy
- mutation of large gene (ATM) on chromosome 11 that is involved in DNA repair and control of the cell cycle
- extremely sensitive to radiation, therefore cant have CT’s
- ataxia, dysarthria, chorea, cranial nerve palsies, diffuse motor and sensory loss
- immunodeficient 2/2 to atrophy of thymus and have INCREASED RISKS OF DEVELOPING INFECTIONS AND LYMPHOMA
- prominent telangiectasias of the sclera and skin
- pulmonary fistula are common; can lead to development of pulmonary infections and abscesses
57
Q
What type of fistulas do patients with ataxia-telangiectasia develop?
A
- pulmonary fistulas
- can lead to pulmonary infections and abscesses
58
Q
Dentatorubropallidosylvian atrophy
A
- autosomal dominant
- trinucleotide repeat, chromosome 12q
- neuronal degeneration in occurs primarily in the dentate nucleus, subthalamic nucleus, red nucleus, and external segment of globus pallidus
- symptoms -> dystonia, ataxia and choreathetosis
59
Q
Machado-Joseph disease
A
- autosomal dominant; trinucleotide repeat disorder CAG (chromosome 14)
- symptoms -> progressive ataxia, ophthalmoplegia, distal motor weakness, hyper-reflexia, mild parkinsonism, bulbar symptoms
- atrophy -> dentate nucleus, spinocerebellar tracts, oculomotor nuclei, anterior horns, pontine nuclei, substantia nigra
- cerebello-olivary system relatively spared
- no effective therapy
60
Q
acute disseminated encephalomyelitis
A
- post-infectious encephalomyelitis
- demyelinating disease that usually follows a viral infection (especially measles) by 4-6 days or vaccination (especially rabies) by 1-2 weeks
- also associated with EBV, CMV, mycoplasma
- monophasic autoimmune attack by T cells against myelin basic protein; perivenular infllamation and demyelination
- symptoms -> fever, headache, nuchal rigidity -> followed by multiple neurological deficits
- most patients recover; 10-20% are left with permanent deficits
61
Q
treatment for ADEM
A
steroids, AEDs, mannitol for cerebral edema
62
Q
Progressive multifocal leukoencephalopathy
A
- subacute demyelinating disease that results from reactivation of JC virus (papovavirus) in immunocompromised patients
- infects oligodendrocytes
- mutlifocal areas of demyelination predominately in the subcortical white matter
- affects 4% of patients with AIDS
- lesions are often in parieto-occipital region, non-enhancing, and have increased signal on T2 and FLAIR; INVOLVES SUBCORTICAL U FIBERS
- symptoms depend on location -> hemiparesis, VF cuts, sensory changes, eventually dementia
- Dx -> biopsy or PCR amplification of JC virus RNA in CSF
- poor prognosis, aproximally 80% die within 9 months
63
Q
Marchiafava-Bignami Disease
A
- results in demyelination of the corpus callosum
- initially described in Italian men who consumed large quanities of cheap red wine, but cause unknown
- necrosis of the medial aspect of the corpus callosum
- results in nonspecific symptoms -> memory loss, confusion, depression, dementia, mutlifocal neurologic signs
- slowly progressive, usually results in death within 3-6 years after symptom onset
64
Q
A
