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
Infantile GM2 Gangliosidosis
- AR
- deficiency B-galactosidase
- cherry red macula, HSM, BONY ABNORMALITIES, **dysmorphic facial features, contractures**
26
Neimann Pick Disease
- 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
Fabry Disease
- 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
Phenylketonuria
- 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
Maple Syrup Urine Disease
- 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
Homocystinuria
- 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
Hartnup disease
- 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
Lesch-Nyhan Syndrome
- 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
Glucose transporter protein syndrome
- 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
Zellewenger Syndrome
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
Wilson Disease
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
Acute intermittent porphyria
- 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
what drugs can cause an acute attack of AIP?
barbituates, benzos, sulfonomides, hormone therapy, low carb intake
38
Hallervorden-Spatz Disease
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
Levine-Critchley syndrome
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
Superficial siderosis
- 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
what type of inheritance pattern do mitochondrial disorders have?
maternal inheritance
42
MELAS syndrome
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
MERRF Syndrome
Myoclonic epilepsy wiht red-ragged fibers
- myoclonic epilepsy, mental deterioration, and proximal myopathy in children or adults
- slowly progressive
44
Kearns-Sayre Syndrome
- 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
Lebers hereditary optic neuropathy
- mitochondrial disorder
- progressive, PAINLESS, central vision loss and cardiac conduction abnormalities usually in the 3rd or 4th decades
46
List mitochondrial disorders
1. MELAS Syndrome
2. MERRF syndrome
3. Kearns Sayre Disease (not maternally inherited)
4. Lebers Hereditary Optic neuropathy
47
Enzyme deficiency thought to cause 20% of ALS
Cu/Zn superoxide dismutatase located on chromosome 21q
48
Amyotrophic lateral sclerosis
- 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
What is spared in ALS?
Extraocular muscles, SENSATION, sphincter function
50
Kennedy' Disease
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
Spinomuscular atrophy type 1
- 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
spinomuscular atrophy type 2
- chronic infantile SMA
- begins between age 6 - 15 months
- AR
- contractures, scoliosis
- survive until 2-4 years of age
53
spinomuscular atrophy type 3
AKA Kugelberg-Welander Disease
- AR
- chronic proximal SMA
- slowly progressive proximal limb weakness
54
Adult-onset SMA
- autosomal dominant inheritance
- patient's survive into 4th to 6th decades
55
Friedreichs Ataxia
- 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
Ataxia-telangiectasia
- 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
What type of fistulas do patients with ataxia-telangiectasia develop?
- pulmonary fistulas
- can lead to pulmonary infections and abscesses
58
Dentatorubropallidosylvian atrophy
- 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
Machado-Joseph disease
- 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
acute disseminated encephalomyelitis
- 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
treatment for ADEM
steroids, AEDs, mannitol for cerebral edema
62
Progressive multifocal leukoencephalopathy
- 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
Marchiafava-Bignami Disease
- 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
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