Heme/Onc/Neuro Flashcards
1
Q
What are the components of the motor neuro exam?
A
Side to side, top to bottom: Tone, Power Cerebellar: Nystagmus Voice UE: FTN, RAM LE: Heel-shin, toe-tapping Trunk; Romberg, tandem gait
2
Q
Following a first unprovoked seizure, what is the risk of epilepsy over the next 5 years?
A
40%
3
Q
Hypsarrhythmia on EEG?
A
Infantile spasms/West syndrome 3-8 M ACTG or Vigabatrin
4
Q
3 Hz spike and wave on EEG?
A
Childhood absence epilepsy 3-8 years Ethosuzimide or VPA
5
Q
Migraine criteria?
A
A. At least 5 attacks B. Headache lasting 1-72 hours C. Two of 1. Bilateral location 2. Pulsating quality 3. Moderate to severe intensity 4. Aggravated by physical activity D. One of 1. Nausea +/- vomiting 2. Photo or Phonophobia
6
Q
What are the characteristics of acute cerebellar ataxia?
A
Post or parainfectious Abrupt onset Trunk affected more than limbs Vertigo Nystagmus Afebrile Normal mental status Imaging normal CSF WBC 0-25 Full recovery 3-6weeks
7
Q
What proportion of childhood cancers are ALL?
A
25%
8
Q
Overall survival of childhood cancer
A
82%
9
Q
CDs to know
A
CD19- B cell CD3- T cell
10
Q
ALL risk
A
Age Presenting WBC Cytogenetics Response to treatment
11
Q
What is the diagnosis in a child with pancytopenia, short stature, abnormal thumbs and hyperpigmentation?
A
Fanconi syndrome Presents around age5
12
Q
What are the two possibilities for anemia and low retics with other normal cell lines in a 1 year old?
A
- Transient erthroblastopenia of childhood (self-limited) 2. Diamond-Blackfan anemia (lifelong)
13
Q
How do you distinguish between TEC and Diamond-Blackfan anemia?
A
DB 1st 6 M, TEC after 1 year DB RBC have fetal characteristics (hbF) Elevated adenosine deaminase in DB
14
Q
What is Kostmann syndrome?
A
Severe congenital neutropenia G-CSF used to elevate counts
15
Q
- Eczema 2. Thrombocytopenia 3. Recurrent resp infections Diagnosis?
A
Wiskott-Aldrich
16
Q
- FTT 2. Chronic diarrhea 3. Neutropenia
A
Schwachman-Diamond syndrome Exocrine pancreatic dysfunction, skeletal ABN, growth retardation, BM insufficiency Often mistaken for CF
17
Q
What is the timing for the physiologic nadir anemia?
A
8-12 weeks 6-8 weeks
18
Q
Three most common causes of eosinophilia?
A
Atopic dermatitis Allergic rhinitis Asthma
19
Q
Marked cyanosis, lethargy with normal O2S?
A
Methemoglobinemia Rx: Methylene blue Hyperbaric Exchange transfusion
20
Q
Platelet problems?
A
Epistaxis, hematuria, menorrhagia, GI hemorhhages
21
Q
Coagulation factor deficiencies?
A
Ecchymoses out of proportion to trauma Delayed bleeding from odl wounds Extensive hemorrhage, particularly into joint spaces
22
Q
Most common bleeding disorders?
A
von Willebrand- AD Factor VIII (Hemophilia A) and Factor IX (B) X linked, A>B
23
Q
What disorder causes elevation of PT when other coagulation testing is normal?
A
Factor VII deficiency
24
Q
Most common initial presentation of hemophilia?
A
Bleeding after circumcision
25
What is von Willebrand factor?
Large multimeric protein that binds to collagen at points of endothelial injury Serves as a bridge between damaged endothelium and adhering platelets Prolonged BT, PTT prolonged, decreased VIII
26
Treatment of vW disease?
DDAVP
27
How likely is a bleeding disorder in a patient with menorhaggia?
20% Most common von Willebrand
28
Vitamin K in coagulation?
Cofacor for II, VII,IX, X Protein C and S
29
How do you distinguish liver vs. DIC vs Vita K deficiency
Factor V- Ab N in liver, N in Vita K Factor VIII- decreased in DIC, normal in others
30
DIC results?
Prolonged PTT Low fibrinogen Platelets low D dimer high
31
What are the AD inherited hypercoagulable states?
Factor V Leiden Protein C deficiency Antithrombin III deficiency
32
At what age does thymic function cease?
Peak mass at 10 years then decreases
33
What are Howell-Jolly bodies?
Absent or reduced splenic function
34
What is the difference between alloimmune and autoimmune?
Alloimmune: antibodies responsibles for hemolysis are directed against another RBCs Autoimmune: antibodies are directed against the hsots red cells
35
Where are platelets produced and how long do they last?
Non-nucleated cells Produced by megakaryocytes Lifespan 7-10 days
36
How does platelet adhesion occur?
Initiated by contact with extravascular components (collagen) facilitated by binding vWF Secretion of mediators cause firm aggregation via fibrinogen binding and increase local vasoconstriction
37
When does bleeding risk occur in thrombocytopenia?
Platelet count falls below 100: increased risk for bleeding Usually \>50 are adequate Plts 10-30 may bleed with trauma
38
What are the characteristics of ITP?
Immune thrombocytopenia purpura Plt usually
39
What are the characteristics of neonatal alloimmune thrombocytopena?
Manifested by isolated, transient but potentially severe thrombocytopenia Due to destruction in plts by maternal alloAB Occurs when fetal plt contain Ag inherited from Dad that Mom lacks Fetal plts cross the placenta and trigger maternal Ab production Most serious complicaiton: ICH Recurrence in future in 75-90% more severe everytime
40
What are the characteristics of neonatal autoimmune thrombocytopenia?
Maternal Ab react with both maternal and infant platelets. Occurs with maternal autoimmune disorders (SLE, ITP) Risk of ICH is greater in allo than auto Nadir is 2-5 days then will usually recover
41
What is Kasabach Merritt syndrome?
Shorterned plt survival caused by sequestration of plts and coagulation activation in large vascular malformations of trunk and extremities
42
What are the mechanisms of thrombocytopenia?
Decreased production Increased destruction Sequestration
43
What are the most common causes of microcytic anemia?
1. Alpha thal trait 2. Beta thal trait 3. Iron deficiency anemia
44
What is HbA?
2 alpha 2 betas
45
HgF
2 alpha 2 gamma
46
HgBart
4 gamma
47
hgH
4 beta
48
How does alpha thal trait present?
2 genes Mild microcytic, hypochromic anemia HbBart present in neonatal period When infant transitions to HgA, less gamma production therefore no more HgBart No treatment
49
How does alpha thalassemia present?
3 genes HgH disease Excess beta globin chains accumulate and form tetramers, making HbH Unstable Hg precipitates in circulating RBC leading to hemolysis
50
What happens with 4 alpha thal genes?
Hydrops fetalis HgBarts predominate. Severe impairment of O2 delivery
51
What is beta thal minor?
Microcytosis and hypochromia but only mild anemia Hb electrophoresis in neonatal period is normal but 1 year HbA2 and HbF are elevated
52
What is beta thal intermedia?
Variety of mutations that cause less signifcant disease than beta thal major
53
What is beta thal major?
2 defective genes and no beta globin is made so no hbA Born healthy with hgF however symptoms at 6 months when transition from HgF to hbA should occur Marked hypochromic, microcytic anemia Chronic transfusions, iron chelation, stem cell transplant
54
What is a TIBC?
Available binding sites for Fe so indirectly measures transferrin
55
What is the starting dose of iron for fe deficiency anemia?
3-6mg/kg/day TID
56
What is G6PD?
Central enzyme of pentose phosphate shunt of glucose metabolism catalyzes conversion of G6P to 6PG and generated NADPH (acts to neutralize agents that oxidize hB) Leading to precipitation of hB and damage to membrane resulting in premature RBC destruction
57
What are the common inheritance of G6PD?
Type A: Most common X linked
58
What are the triggers for G6PD?
Meds: sulfa septa, macrobid, antimalarials, vita K, methylene blue, ASA
59
What are the types of hemophilia?
A-Factor VIII B-Factor IX
60
What are the first signs of hemophilia?
Easy bruising Mucosal bleeding
61
What are the classic signs of hemophilia?
Soft tissue bleeding and hemarthroses Hallmark: Bleeding into joints
62
What is the typical trigger for coagulation?
Tissue Factor
63
What is the severity rating for hemophilia?
Mild \>5% Moderate 1-5% Severe
64
Leading cause of death in hemophilia?
intracranial hemorhage
65
What are the possible treatments for hemophilia?
Factor replacement DDAVP
66
What is the most common inherited bleedng disorder?
vwd
67
How is vwd inherited?
AD
68
What happens in vWD?
Decreased quantity or activity of vWF Protein is essential for primary platelet hemostasis and fibrin clots
69
How do you investigate for VwD?
Ristocetin activity: good for evaluating for vWF function VwF Ag: immunoassay, quantititave PTT: mildly prolonged in 50% of vWD
70
What is the treatment for vWD?
Desmopressin: Increases vwF, factor VIII and ROC activity in types 1 and 2 vWF containing factor VIII concentrates: Needed in type 3 disease
71
Which species of malaria is sickle protective for?
Falciparum
72
What is the pathology of sickle cell disease?
Replacement of hydrophilis glutamine acid with hydrophobic valine which alows HbS to polymerize in the deoxygenated state
73
What encourages sickling?
Low O2 Low pH increased HbS
74
Most common forms of childhood cancer?
1. ALL 2. AML 3. CML
75
Disorder with the highest rate of leukemia?
Downs
76
What are the risk factors for ALL?
10Y WBC \>50 Philadelphia chromosome
77
What are the genetic syndromes associated with Wilms?
WAGR: Wilms, aniridia, GU anomalies, DD Denys Dash: Nephrotic syndrome, gonadal dysgenesis, renal failure Hemihypertrophy Beckwith Weidemann
78
What is the most common initial presentation of lymphoma?
Painless LN
79
How frequent is mediastinal involvement in lymphoma?
2/3
80
What are the predisposing conditions for lymphoma?
Wiskott Aldrich SCID CVID I linked lymphoproliferative syndrome Ataxia telangiectasia
81
Hallmark of Hodkins lymphoma?
Reed Sternberg cells
82
What are the lab findings in tumor lysis syndrome?
HyperUric HyperK HyperPO4 HypoCA
83
What is the management of tumor lysis syndrome?
1. Hyperhydration 2.Reduce uric acid: Allopurinol, Rasbuicase 2. Urinary alkalination 4. K: limit K intake, treat as needed 5. Supplement only if symptomatic 6. PO4
84
What is aFP?
Alpha fetoprotein Glycoprotein normally synthesized by fetal yolk sac Increased in acute liver disease, ataxia telangiectasia, typrosinemia Tumor marker: epithelial liver tumors, yolk sac, embryonal carcinomas
85
What is BHCG?
Glycoprotein produced by tropholblasts of the placenta to stimulate hormones and maintain pregnancy Increased in renal insufficiency, malignant germ cell tumors
86
What is the most common cancer of young men?
Testicular cancer 40% Seminomas
87
What are the risk factors for testicular cancer?
Cryptocordism, gonadal dysgenesis, Klinefelter
88
What is the most curable cancer of childhood when detected early?
Retinoblastoma
89
What are the common clinical findings in retinoblastoma?
Leukocoria Strabismus Proptosis, periorbital erythema, visual loss
90
What is methotrexate?
Antimetabolite Competitive inhibition of folic acid Cannot make nucleic acids Inhibits cycle in ALL rapidly diving cells Leukovorin added to protect healthy cells
91
What are nucleotide analogs?
5fluruoracil, 6 MP, Cytobaraine Almost identical to nucleic acids, therefore gets taken up and stops cell replication SE: Rash, myelosuppression
92
What are microtubule inhibitors?
Inhibits microtubular assembly, disrupts cell transport VIncristine, vinblatin SE: Neuropathy, skin burn
93
What are anthrocyclines?
Inhibit DNA polymerase and ribosomes Doxorubicin, duanorubicin, actinomycin SE: Cardiotoxicity and myelosuppression
94
What are topisomerase inhibitiors?
Help unwind DNA, therefore cannot unwind Eg Etoposides
95
What is the role of platinum based chemo therapy?
Cisplatin and carboplatin gets into DNA helix and binds it soit can't uncoil
96
What are the main concerns about longterm outcomes in cancer?
1. Neurocognitive 2. Cardiotoxicity 3. Endocrinopathies 4. Secondary malignancies
97
What are the non-infectious complications of blood transfusions?
1. Bacterial sepsis 2. TRALI 3. Febrile nonhemolytic reactions 4. Allergic reactions 5. Immediate hemolytic reactions 6. Delayed hemolytic reactions
98
What is the basis of febrile nonhemolytic reactions?
Cytokine release from donor WBCs due either to prolonged storage or recipient AB against donor WBCs
99
What is t cyclic vomiting syndrome?
Characterized by repeated episodes of nausea and vomiting lasting for hours to days Separated by symptoms free periods
100
What is abdo migraine?
Recurrent episodes of abdominal pain, typically midline or poorly localized, dull and mod to severe intenity abdo pain is associated with two additional features: Anoreixa, nausea, vomiting, pallor
101
What are the options for abortive therapy in migraines?
Triptans NSAIDS Anti-emetics Dyhydroergotramine
102
What are features suspicious of neurodegenerative disorders and not CP?
Regression of milestones Family history of neuro conditions Ataxia, involuntary movements, oculomotor abN, muscle atrophy, sensory loss Hypotonia Rapid deterioration of neuro sgins Marked worsening during periods of catabolism
103
What is ADEM?
Symptoms of encephalopathy including fever, vomiting, headache and meningismus Symptoms peak by 4-7 days often with altered LOC Associated with: Long tract pyramidal signs, acute hemiparesis, cerebellar ataxia, cranial neuropathies
104
What is the gene that causes muscular dystrophy?
Dystropin First sign: weakness
105
What are the clinical findings in duchenne muscular dystrpophy?
Weakness Difficulty with running, jumping and walking up steps Waddling gait, lumbar lordosis, calf enlargement Positive gowers sign
106
What is the natural history of DMD vs. BMD?
DMD: Confined to wheelchair by age 12, die in late teens/tweenties BMD: Ambulatory beyond 16, survive beyond 30
107
What is FrederichAtaxia?
-AR degenerative d/o -degeneration and sclerosis of spinocerebellar tracts, posterior column, corticospinal tracts -progressive ataxia -absent DTR -kyphoscoliosis -nystagmus -pes cavus (high arch) -abnormal ECG
108
Crouzon Syndrome ?
premature craniosynostosis and is inherited as AD trait
109
Apert syndrome
Associated with premature fusion of multiple sutures, including the coronal, sagittal, squamosal, and lambdoid sutures. Characterized by syndactyly of the 2nd, 3rd, and 4th fingers,
110
Rett syndrome
Normal dev until 6 months, then regression 6m-3yrs, then deceleration of head growth with stereotypical hand mvts, severe DD, gait ataxia and apraxia
111
Drug of choice for absence epilepsy?
Ethosuximide Valproate Lamotrigine
112
What s the most common brain lesions seen on MRI in CP?
PVL
113
What is the POSTER criteria for CP?
Posturing/AbN movements Oropharyngeal porbelms Strabismus Tone Evolutional maldevelopment Reflexes
114
What is the most common cause of neonatal asymmetric crying facies?
Congenital absence of depressor anguli oris muscle
115
What is rolandic epilepsy?
Schoo age childn Facial paresthesia or twitching and drooling followed by hemiclonic movements
116
What is the typical EEG of absence seizures?
3Hz spike wave pattern Activated by hyperventilation
117
What type of seizures presents with brief, bilateral, intermittent jerking like a parent?
Juvenile myoclonic epilepsy Fast 3-5 Hz spikes AD inheritance
118
What is the triad of infantile spasms?
1. Spasms. 2. HYpsarrhythmia 3. Developmental regression
119
What is the likelihood of reccurence of febrile seizures?
30%
120
What makes a febrile seizure complex?
Lower temp at presentation Focal features Extended duration Occuring more than once in a day
121
What is the risk of epilepsy after a febrile seizure?
2%
122
What are the three most common neurocutaneous syndromes?
1. Neurofibromatosis: AD 2. Tuberous sclerosis: AD 3. Struge webber:Sporadic
123
What is the main triad of TSC?
Seizures Mental retardation Facial angiofibroma
124
What is incontinentia pigmenti?
X linked dominant disorder 100% female Associated with seizures and MR Lines of blisters on trunk and extremities then progress to brown hyperkeratotic lesions then whorled, swirling, macular lines
125
Pancytopenia +short stature +abN thumbs + hyperpigmentation
Fanconi anemia Numerous physical abN often present at birth Anemia at 5 years Chromomsal breakage analysis
126
DIC labs
PT/PTT Prolonged Fibrinogen LOw Platelets Low D-Dimer HIGH
127
Predisposition to thrombosis?
Factor V Leiden- AD, incomplete penetrance Protein C- AD Protien S Antithrombin III deficinecy-AD ALL AB
128
In Sturge-Weber syndrome, where is the usual location of a Port-Wine stain?
Distribution of the first branch of the trigeminal nerve (ophthalmic branch)
129
What are the 3 clinical features of Sturge-Weber syndrome? -what is the classic finding on CT head of a patient with Sturge Weber who is coming in with focal seizures?
\*\*\*Think vascular anomalies! 1. Port-Wine stain 2. Leptomeningeal vascular anomalies - can cause seizures and developmental delay 3. Glaucoma: secondary to ocular vascular anomalies -classic CT finding: intracranial calcification in railroad track/tram track appearance (leptomeningeal vascular anomalies of the cerebral cortex)
130
What is the classic presentation of a pediatric stroke?
Focal weakness of an extremity, often followed by a focal seizure since most strokes involve the MCA territory -Todd's paresis: focal weakness occurs AFTER the seizure -Stroke: focal weakness occurs BEFORE the seizure
131
What is the definition of epilepsy?
Occurrence of 2 or more unprovoked seizures
132
By definition, how long can a Todd's paresis last up until?
24 hours maximum
133
What is BECTS?
Benign Epilepsy of Childhood with Centrotemporal spikes aka Benign Rolandic Epilepsy
134
What test should be done in all patients with new onset focal seizures?
MRI - urgency will depend on presence of other red flags
135
In a patient presenting with their first unprovoked seizure, what are the chances of having another seizure in the future?
30%-40%
136
What are characteristic features of BECTS? (4) Common trigger? Treatment?
1. Occur at night 2. Partial seizure with no loss of consciousness - however, in 1/3 of patients seizures will progress to secondary generalized 3. Unilateral sensorimotor involvement of the face: tongue, lip, gums, cheeks 4. Inability to speak: gurgling, grunting Common trigger: sleep deprivation Treatment: most do not require antiepileptic therapy since seizures are generally short lived and infrequent -If treating: can use carbamazepine or clobazam
137
What is the natural history of BECTs?
Usually resolve 2-4 years from onset. 95% outgrow by age of 15, 100% outgrow by age of 18
138
What is the most common idiopathic epilepsy syndrome in children?
BECTS
139
What is the peak onset of BECTS? More common in boys vs. girls?
8-9 years old More common in boys
140
Differentiate tics from stereotypies?
Tics: asymmetric, occur when bored or distracted (not excited), onset at 4-5 years old, worsen with time into different movements, semivoluntary Stereotypies: usually symmetric, occur when excited or happy, same movement over time
141
Ways to check for tremor on exam?
Ask patient to pour water from one cup to another Ask patient to draw spirals on piece of paper Ask patient to touch their two index fingers together
142
What does Romberg check for? Pronator drift?
Romberg - propioception Pronator drift - UMN weakness
143
2 features of essential tremor? 2 conditions to rule out?
Worsens with age Occurs with certain postures Does not occur at rest Rule out hyperthyroidism and Wilson's disease (ceruloplasmin)
144
What is holoprosencephaly?
Cephalic disorder in which the forebrain fails to develop into two hemispheres. -can be mild or severe (leads to fetal demise) -midline defects can be seen (cleft palate, midline incisor, anosmia -cyclopsia is most severe form
145
What is the definition of status epilepticus?
Seizure \> 30 minutes OR 2 or more seizures without return to baseline mental status
146
What are the clinical features of tuberous sclerosis? -mode of inheritance
Think ASHLEAF, hamartomas in multiple organs, autosomal dominant of variable penetrance A = ashleaf hypopigmented macule seen with Woods Lamp S = shagrene patch (area of thick leathery skin) H = heart rhabdomyoma L = lung hamartoma, retinal hamartoma E = Epilepsy from brain tubers A = Angiomyolipoma of the kidney F = Facial angiofibromas Can also get periungual fibromas (major criteria), subependymal giant cell astrocytomas Infantile spasms may be the first recognized clinical manifestation of tuberous sclerosis (occur 6-12 mo, almost never occur \> 12 mo) (65-70% of cases) -indicate poor neurodevelopmental outcome
147
Which conditions are associated with: -hypopigmented macules -hyperpigmented macules
Hypopigmented macules: tuberous sclerosis Hyperpigmented macules: neurofibromatosis-1
148
What is the triad of clinical features seen in the Miller Fisher variant of Guillain Barre syndrome?
1. Ophthalmoplegia 2. Ataxia 3. Arreflexia
149
What is the diagnostic criteria for neurofibromatosis type-1?
COLOR-NF Need 2/7 of the following: Cafe au lait spots - minimum of 6 \> 5 mm in prepuberty and \> 15 mm in postpuberty Optic glioma Lisch nodules - hamartomas of the iris (almost never seen in children
150
What is the pathophysiology of Guillain-Barre syndrome? -how do you diagnose GBS?
Postinfectious polyneuropathy due to antibodies attacing myelin sheath causing demyelination -follows a nonspecific viral infection by 10 d -always affects motor nerves, sometimes autonomic nerves (arrhythmia, hyper/hypotension, bowel or bladder dysfunction), and only sometimes sensory nerves -diagnosis: CSF studies are essential, MRI spinal cord to rule out other spinal cord lesions that may also cause paralysis, nerve conduction studies, EMG, can also send stool samples for Campylobacter or H pylori
151
What do you see in CSF of a patient with guillain barre syndrome?
Usually either completely normal or see isolated elevated proteins -NO pleocytosis (this is diagnostic of GBS since in any other cause like infection, if proteins go up, you would ALSO see a cellular response with pleocytosis)
152
What are 2 MRI findings generally seen on imaging of guillain barre syndrome patients?
With gadolinium enhancement: 1. Thickening of cauda equina 2. Thickening of intrathecal nerve roots
153
What is the management of a patient with guillain barre syndrome? -prognosis?
1. Admit to hospital and monitor closely since ascending paralysis can rapidly involve resp muscles within 24 hrs 2. Use spirometry to monitor lung capacity 3. IVIG x 5 days 4. May need to keep patient NPO if bulbar muscles are affected (difficulty speaking or swallowing leading to increased risk of aspiration) -prognosis: spontaneous recovery within 2-3 wks with return of full strength usually
154
What 3 clinical features are predictive of poor outcome in guillain barre syndrome?
1. Need for intubation 2. Cranial nerve involvement 3. Maximum disability at time of presentation
155
What are the main etiologies of cerebral palsy? (3)
1. Prenatal insult (80%): maternal infection most common leading to abnormal brain development 2. Intrapartum asphyxia ( 97th percentile)
156
What are the classifications of cerebral palsy? (4) -most common? -what are the usual findings on MRI for each? -what are the usual causes for each?
1. Spastic diplegia (35% = most common) -MRI findings: PVL, periventricular cysts or scars in white matter, ventricular enlargement -major causes: damage to the white matter due to prematurity, ischemia, infection, endocrine/metabolic (thyroid) 2. Spastic quadriplegia (20%): -MRI findings: PVL, multicystic encephalomalacia -causes: ischemia, infection, endocrine/metabolic/genetic/developmental 3. Hemiplegia (25%): -MRI findings: in utero or neonatal stroke -causes: thrombophilic disorders, infection, genetic/developmental/periventricular hemorrhagic infarct 4. Extrapyramidal (athetoid, dyskinetic) (15%): -MRI findings: asphyxia = symmetric scars in putamen and thalamus, kernicterus = scars in globus pallidus and hippocampus, mitochondrial = scars in globus pallidus, caudate, putamen, brainstem -causes: asphyxia, kernicterus, mitochondrial, genetic/metabolic
157
What is the usual clinical presentation of infants with spastic hemiplegia?
1. Decreased spontaneous movement on the affected side 2. Hand preference at very early age 3. Arm involvement \> leg involvement 4. Spasticity in affected side (increased muscle tone especially in antigravity muscles like gastrocnemius which increases with velocity) = usually walks on tiptoes, flexed wrist
158
What is the most common neuropathologic finding in children with spastic diplegia?
PVL (seen on MRI in \> 70% cases)
159
What is the most severe form of CP and what are the clinical features?
Spastic quadriplegia: 1. marked motor impairment of all extremities 2. High association with MR, seizures 3. Swallowing difficulties are common increasing risk of aspiration pneumonia 4. Speech and visual abnormalities
160
What are the clinical features of athetoid CP?
1. Hypotonic with poor head control and marked head lag --\> develop increased tone with rigidity and dystonia over several years 2. Upper extremities \> lower extremities with limb positioning in fixed postures 3. Tongue thrust/drooling 4. Upper motor neuron signs are usually not present, seizures are uncommon 5. Intellect preserved in many patients
161
Which form of CP is most likely to be associated with birth asphyxia?
Athetoid CP
162
In patients with dystonia who have a normal MRI, what condition should you rule out?
Segawa disease: DOPA-responsive dystonia! -may LOOK like athetoid CP but when you give DOPA, they then develop normally and the symptoms resolve
163
What tests should be ordered for work-up of a patient with possible CP? (6)
1. MRI head 2. MRI spine (r/o abnormalities at the base of the skull, spinal cord tumor) 3. Metabolic work-up 4. Hearing/vision tests 5. Genetic testing if other congenital malformations are present 6. For hemiplegia, need coags/thrombosis work-up to r/o stroke
164
What are main treatment modalities for children with CP?
1. Multi-D team function: PT/OT/dietician/SLP/social workers 2. Exercises to decrease contractures 3. Ortho referral: may require tenotomy of achilles tendon, etc. 4. Motorized wheelchairs, special feeding devices, etc. 5. Constraint-induced movement therapy: useful in hemiplegic CP where the good side is constrained with casts while the impaired side performs exercises to improve hand and arm functioning 6. Medications to treat spasticity: benzos, baclofen, dantrolene, levodopa for dystonia, botox injections into specific muscle groups or salivary glands
165
What are the most common causes of recurrent headaches in children and adolescents? (2)
1. Migraine 2. Tension
166
What is spina bifida occulta? -what is occult spinal dysraphism?
Midline defect of the vertebral body WITHOUT protrusion of the spinal cord or meninges -usually asymptomatic -usually a defect in posterior vertebral body fusion -occult spinal dysraphism: cutaneous manifestations (hemangioma, discoloration of the skin, pit, hairy patch) overlying closure defect of the posterior vertebrae (L5-S1 most commonly) and can be associated with developmental abnormalities of the spinal cord (tethered cord for example)
167
What are options for prophylaxis of migraines? (6) -indication for use?
Indications for use: 1. Need for abortive medication \> 3x/wk 2. Missing lots of school or lots of functional impairment Good evidence: 1. Flunarizine (calcium channel blocker) Poor evidence but used anyway: 2. Tricyclic antidepressants: amitryptiline 3. Anticonvulsants: topiramate, valproic acid, levetiracetam 4. Beta blockers: propranolol 5. Calcium channel blockers: verapamil 6. SSRIs: fluoxetine
168
What drugs can cause movement disorders? (3)
1. Antipsychotics 2. Anti emetics (metochlopramide) 3. Anti histamines (cetirizine)
169
What are signs/symptoms of acute dystonic reaction? (2) -treatment?
Caused by too much dopamine blockade usually by an antipsychotic, thus leading to uninhibited cholinergic activation 1. Torticollis 2. Tongue protrusion -treatment: anticholinergic! 1st line = benzatropine (Cogentin), 2nd line = benzos, 3rd line = IV benadryl
170
What are clinical features of neuroleptic malignant syndrome? (4)
1. Dystonia 2. Fever 3. Muscle rigidity 4. Autonomic symptoms: tachycardia, hypertension
171
What is the most common cause of chorea in children? -what are the clinical hallmarks of SC? -what is the treatment?
Sydenham's chorea -emotional lability is CHARACTERISTIC of sydenham's chorea -clinical hallmarks: 1. Chorea 2. Hypotonia 3. Emotional lability\*\*\*\* (this is super characteristic) -treatment: PENICILLIN x 10 d course (to decrease risk of rheumatic fever), steroids, then long term penicillin prophylaxis, ECHO to r/o carditis
172
What is the order of which the primitive reflexes disappear?
-stepping reflex: 2 mo -grasps: 2-3 mo -atonic neck reflex: 4-6 mo -moro: 4-6 mo -babinski becomes downgoing: 1 yo
173
What are the clinical features of pseudotumor cerebri? -imaging results? -LP results? -causes? (5)
1. Headache 2. 3rd or 6th nerve palsy 3. Papilledema 4. Diplopia -imaging: MRI/CT normal -LP normal except for increased opening pressure -causes: 1. Medications 2. Hyperparathyroidism/hypothyroidism 3. Cushing's syndrome 4. Obesity 5. Sinus venous thrombosis
174
What medications can cause pseudotumor cerebri? (6)
1. Tetracyclines (minocycline) 2. Cyclosporine 3. Steroids 4. Nitrofurantoin 5. High vitamin A 6. Growth hormone supplementation
175
What is the treatment for pseudotumor cerebri?
1. Removing any offending drugs 2. Weight loss 3. Acetazolamide or topamax 4. Therapeutic LPs for severe
176
What are side effects of phenytoin?
1. Hypotension 2. Fulminant hepatic failure 3. Lymphadenopathy 4. Stevens-Johnsons
177
Which two medications can increase serum phenytoin serum levels?
1. Warfarin 2. Septra (decreases metabolism of phenytoin) \*\*\*decreases metabolism of dilantin by decreasing P450 enzyme activity
178
What percentage of children with absence seizures develop GTC seizures?
40-50%
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What factors determine good prognosis for absence seizures (aka resolution)? (5)
1. No GTC seizures 2. Developmentally normal 3. Normal neurological exam 4. No family history of seizures 5. Normal EEG
180
What 3 medications can be used to treat absence seizures?
1. Ethosuxamide (best choice) 2. Valproic acid 3. Lamotrigine
181
What criteria must be fulfilled to make the diagnosis of chronic daily headache (CDH)?
1. \> 4 month history 2. \> 15 headaches/month 3. Headaches last \> 4 hours -normal neuro exam
182
What are the main distinguishing features between tension-type headaches and migraines?
Tension type headaches: -usually mild -do not disrupt patient's lifestyle or activities -no N/V/photophobia Migraines: -stereotypes attacks of frontal, bitemporal or unilateral intense pounding or throbbing pain that is aggravated by activity and disrupt patient's lifestyle or activities. Improved with rest. -associated with N/V/photophobia/phonophobia -can have visual aura preceding the headache and last 15-30 mins
183
What are indications for neuroimaging in a patient presenting with headache? (8)
1. Most severe on awakening or am vomiting 2. Focal neuro signs/papilledema on exam 3. Awaken the patient from sleep 4. Altered LOC 5. Seizure 6. Exacerbated by bending or coughing 7. Acute, severe without previous history of headache 8. Progressively worsenin
184
What are clinical features of SUNCT? -workup? -treatment?
Short lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing: 1. Severe neuralgiform pain of very short duration = painful paroxysms felt in or around the eye in V1 distribution of trigeminal nerve 2. 2-600 times per day 3. Ipsilateral conjunctival injection and tearing very prominent Workup: need MRI brain in every case due to secondary causes of SUNCT from pituitary tumor Treatment: 1. Oxygen for pain relief 2. Trials of indomethacin 3. May need carbamazepine or lamotrigine
185
What therapies can be used for acute treatment of migraine?
1. Biobehavioural: -regular sleep schedule -regular dietary schedule (avoid missing meals) -hydration -elimination of precipitating factors -biofeedback -psychotherapy 2. Medications: -Analgesics (NSAIDs, acetaminophen) -triptans (intranasal sumatriptan has good evidence but can only be used in children \> 12 yo) -antiemetics (metoclopramide, promethazine, ondansetron)
186
What is the definition of partial vs. primary generalized seizure? -in a patient who is found during a generalized seizure, what one feature can help you determine whether the seizure was primary generalized vs. focal with secondary generalization?
Partial: sz arises from one region of the cortex -remember that partial seizures can become secondary generalized once the electrical conduction spreads from one hemisphere to the other Generalized: sz arises from both hemispheres simultaneously -primary generalized vs. secondary generalized: if the child is verbal, they MAY be able to tell you they had an aura prior. Presence of an aura indicates a focal origin
187
What are uncinate seizures? -gelastic seizures?
Uncinate seizures: arise from medial temporal lobe with an olfactory hallucination of an extremely unpleasant odor (burning rubber) -gelastic seizures: originate from hypothalamic tumor, spells of uncontrolled laughter
188
What is the characteristic EEG finding of absence seizures? -what maneuvers can provoke absence seizures? (2)
3-Hz spike and wave activity -stimulated by hyperventilation or strobe light stimulation
189
How can you differentiate between absence seizures (generalized) versus complex partial temporal seizures?
Both cause cessation of activity, staring spells, and automatisms -Absence seizures: no postictal confusion, simple automatisms, provoked by hyperventilation, last a few seconds -Complex partial temporal seizures: + postictal confusion, more complex automatisms, last several minutes \*\*\*\*Impt to differentiate between these since anticonvulsant treatment is different!
190
What is the cause of benign neonatal convulsions?
Autosomal dominant genetic disorder localized to chromosome 20 -get generalized clonic seizures towards the end of the 1st week of life -favorable prognosis
191
What are the clinical features of juvenile myoclonic epilepsy (classic triad)? Classic hallmark feature? -treatment?
Autosomal dominant disorder -occurs in adolescence -classic triad: 1. Myoclonic jerks 2. GTC sz 3. Absence sz -classic hallmark feature: morning myoclonus within 90 minutes of awakening (could be described as clumsy with difficulty combing hair or dropping fork) -treatment: valproic acid
192
What are potential causes of infantile spasms? -which are more likely to respond to therapy? -what is the most recognized cause? -what treatment is used to treat infantile spasms? (4)
1. Idiopathic = 40% of cases = MORE LIKELY TO RESPOND TO THERAPY and 40% have good intellectual outcome 2. Specific etiology = 60% of cases = LESS LIKELY TO RESPOND TO THERAPY and have poor intellectual prognosis -metabolic disorders -developmental malformations (polymicrogyria, lissencephaly, schizencephaly, Down syndrome) -Neurocutaneous syndromes (Tuberous sclerosis is the most common recognized cause), sturge weber -Congenital infections -encephalopathies Treatment: 1. ACTH 2. Vigabatrin 3. Benzos 4. Valproic acid
193
What is Lennox-Gastaut syndrome?
Epileptic syndrome = multiple seizure types -most children have underlying brain injury or malformations -usually respond poorly to treatment
194
What is Landau-Kleffner syndrome? -EEG findings? -treatment?
Acquired epileptic aphasia -abrupt loss of previously acquired language in young children due to acquired cortical auditory deficit (will become oblivious to everyday sounds) -some patients develop several types of seizures as well -EEG is highly abnormal in language areas sleep (perisylvian region) especially during NREM -treatment: valproic acid is treatment of choice. Can also try keppra or steroids if prolonged course, speech therapy
195
What is Rasmussen encephalitis? -treatment?
Chronic, progressive focal inflammation of the brain -unknown cause -begins with focal motor seizures, then progresses to hemiplegia and cognitive deterioration -treatment: hemispherectomy
196
What factors increase the risk of development of epilepsy after a febrile seizure? (4)
1. Complex febrile seizure 2. Developmental delay 3. Family history of seizures 4. Abnormal neuro exam -2% chance if one risk factor present -10% chance if two risk factors present
197
What is the recurrence risk for 2nd seizure if a patient presents with a 1st seizure of GTC? -recurrence risk for 2nd seizure if a patient with preexisting neurologic abnormality has a partial seizure and an abnormal EEG?
-1st seizure being GTC: 50% = can wait to start antiepileptics -1st seizure being partial in preexisting neurologic abnormality with abnormal EEG: 75% = start antiepileptics
198
Which anti epileptics should be used for treatment of generalized motor seizures? (4)
1. Valproic acid 2. Lamotrigine 3. Topiramate 4. Levetiracetam
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What anti epileptics should be used for treatment of partial seizures? (5)
1. Carbamazepine 2. Oxcarbazepine 3. Phenytoin 4. Phenobarb 5. Gabapentin
200
Which epilepsy conditions generally require anti convulsant therapy for life?
1. Lennox Gastaut 2. Juvenile myoclonic epilepsy 3. Atypical absence seizures
201
What is transverse myelitis? -clinical features? -workup? -treatment?
Acute postinfectious demyelination of the spinal cord (usually viral) -can also occur post immunization -will have a clearly defined sensory level of deficits (sensorimotor and autonomic) -clinical features: neck or back pain, then numbness and paralysis in the affected musculature with urinary retention/bowel incontinence -workup: need to do CSF (will see pleocytosis and elevated IgG) and MRI (gadolinium-enhancing cord lesion) -treatment: high dose steroids
202
What is a disease of the anterior horn cell? -clinical features of SMA 1, SMA 2, SMA 3?
Spinal muscular atrophy -progressive degeneration of anterior horn cells and denervation of muscle -SMA-1 (Werdnig-Hoffman disease) = severe infantile form (severe hypotonia, affected at birth and progress to flaccid quadriplegia with bulbar palsy, respiratory failure and death within 1st year of life -SMA-2: late infantile form -SMA-3 (Kugelberg-Welander disease): most mild form, begins in late childhood with proximal weakness and progresses slowly over decades \*\*\*Children with SMA have muscle fasciculations due to denervation (see best in tongue) \*\*\*\*Children with SMA are thought to have higher than normal intellect for their age because the effort that they cannot put into physical activities is redirected to intellectual and language development :) Also, they are exposed to adult speech more often due to the social repercussions of the disease :(
203
What do fasciculations represent? -UMN or LMN?
Fasciculations: specific clinical sign of muscle denervation! -sign of LMN lesion
204
What does EMG of SMA patient show? -what is the definitive diagnostic test for SMA? -what is the treatment for SMA? (5 main concepts)
Fasciculations and fibrillations -definitive diagnostic test: specific DNA probe for SMA in the SMN gene -treatment: no treatment is available to delay progression :( All we have is supportive care 1. Minimize contractures 2. Prevent scoliosis 3. Prevent aspiration 4. Maximize social/language/intellectual skills 5. Manage respiratory infections with chest physio, pulmonary toileting
205
What diagnostic tests can be ordered for a possible LMN lesion (anterior horn cell, peripheral nerve, NMJ, muscle)? (3)
1. CK 2. EMG 3. Muscle biopsy
206
What are the 3 peripheral nerve diseases in childhood?
1. Guillain-Barre syndrome 2. Hereditary motor sensory neuropathy (Charcot-Marie Tooth disease) 3. Tick paralysis
207
What are the main clinical features of Charcot-Marie-Tooth disease (hereditary motor sensory neuropathy)? (3
1. Pes cavus deformity of the feet (high arched) 2. Bilateral weakness of dorsiflexion 3. Eventually develop weakness and atrophy of the entire lower legs
208
What are often the earliest signs of myasthenia gravis? (2)
Ptosis and extraocular muscle weakness -older children may complain of diplopia -young children may hold their eyes open with their fingers
209
What is the 2 diagnostic tests for myasthenia gravis?
1. IV edrophonium chloride (tensilon) -acetylcholinesterase inhibitor = blocks the enzyme so that more acetylcholine can bind to the few receptors that aren't blocked by the auto-antibodies -see a transient improvement in strength and decrease in fatigability 2. EMG: decremental response is seen to repetitive nerve stimulation = fatigable weakness \*\*\*muscle biopsy is not needed in most cases
210
A baby is born to a mother with myasthenia gravis. She exhibits generalized hypotonia and inability to suck. How do you confirm the diagnosis? What is your management? When can you expect resolution?
Infants born to moms with MG are affected because mom's auto-antibodies cross the placenta. -Confirmation of diagnosis: administer IM neostigmine and watch for improvement -Treatment: oral pyridostigmine or neostigmine 30 minutes before feeding until resoltuion occurs -Resolution: approximately 3 wks (up to 10 wks)
211
What is the treatment of myasthenia gravis?
1. Cholinesterage inhibitors: neostigmine IM q4-6 hr and before meals to improve swallowing 2. Steroids 3. Thymectomy (especially in patients with high titers of anti-Ach receptor antibodies) 3. IVIG 4. Plasmapheresis
212
What clinical features on exam can be seen in Duchenne muscular dystrophy?
1. Gower sign 2. Calf hypertrophy 3. Proximal leg weakness 4. Hyperlordosis 5. Waddling gait
213
What investigations should be ordered to diagnose Duchenne muscular dystrophy? Which is gold standard for diagnosis?
1. Elevated serum CK 2. DNA probe - GOLD STANDARD - diagnostic -look for duplication or deletion of exons within DMD gene (will get an answer with this 70% of the time) -if duplication/deletion testing is negative, then should sequence the DMD gene \*\*Muscle biopsy with muscle fiber degeneration and increased connective tissue -only do this if the genetic tests are negative!!!!
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What is the inheritance pattern of myotonic muscular dystrophy (ie. Steinert disease)?
Autosomal dominant CTG triplet repeat on chromosome 19
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A teenager presents to you with progressive distal extremity weakness and myotonia (difficulty with muscle relaxation). He is also found to have cardiac arrhythmia, cataracts, male pattern baldness and hollowing of muscles around temples, jaw and neck. His face is expressionless with a tented mouth. What is the diagnosis?
Myotonic dystrophy
216
What are the clinical features of malignant hyperthermia? (6) -drugs that are ABSOLUTELY contraindicated in malignant hyperthermia? (2) -treatment? (3)
1. Rapid increase in body temp (fever) 2. Rapid increase in CO2 (due to increased metabolic rate) 3. Muscle rigidity 4. Cyanosis/hypotension 5. Arrhythmias 6. Seizures Drugs that are ABSOLUTELY contraindicated since they can trigger malignant hyperthermia reaction: 1. Succinylcholine 2. Inhalational anesthetics Treatment: 1. IV dantrolene (muscle relaxant) 2. Sodium bicarbonate 3. Cooling
217
What are the characteristic features of seizures seen in Panayiotopoulos syndrome? -timing? -duration of seizure?
Predominant autonomic symptoms with ictal emesis -always include in ddx for conditions like syncope, migraine, cyclic vomiting, motion sickness, etc. -timing: usually occur at night -duration: usually: \> 5 minutes
218
What are the characteristic features of seizures seen in idiopathic childhood occipital epilepsy (Gastaut type)? -timing? -duration?
Brief, frequent occipital seizures with visual blindness and hallucinations -timing: usually occur during the day -brief
219
What is the diagnostic criteria for Tourette syndrome? (3) -male:female ratio?
1. Must include both motor AND vocal tics 2. Occurs over the period of 1 year with no more than 3 consecutive tic-free months 3. Onset prior to age 18 yo \*\*\*Male:female ratio for TS: 4:1
220
What are 2 common comorbid conditions seen with Tourette Syndrome?
1. ADHD (50% of children with TS) 2. OCD (33% of children with TS)
221
How can you distinguish between tics versus true involuntary movement disorders (ie. chorea or myoclonus)? (2)
With tics: 1. Presence of premonitory sensory urge that is then relieved by the tic 2. Ability to suppress tics voluntarily
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What are the treatment options for tics? (2)
1. Behavioural approach: comprehensive behavioural intervention for tics (CBIT) 2. Medication: based on tic severity, functional interference, self-injurious aspects, etc. -no meds eliminate tics completely, just reduce to a state of tolerable function -first line: clonidine (alpha 2 adrenergic agonist) -second line: atypical neuroleptics (risperidone)
223
What are the 4 types of skull fractures and management of each?
1. Linear = no treatment 2. Diastatic (spreads apart sutures) = no treatment 3. Compound (bone fragments breaking the skin surface) = EMERGENT SURGICAL DEBRIDEMENT but no prophylactic antibiotic therapy 4. Depressed (edge displaced inferiorly) = if \> 0.5-1 cm, need surgical elevation of bone fragments and repair of associated dural tears \*\*\*Any time you see a skull fracture, be concerned that the force was high enough to produce a possible underlying hematoma -don't forget tetatnus prophylaxis
224
An infant presents to you a few weeks after a fall from the changing table with a soft, pulsatile palpable scalp mass. What is your diagnosis?
Leptomeningeal cyst: rare complication of linear skill fracture with separation of the edges of the fracture and laceration of the dura. The arachnoid membranes can then be trapped between the edges of the fracture and results in herniation of fibrotic tissue/meninges/brain to form a soft tissue mass. -requires surgical excision of abnormal tissue and dural repair
225
What is a CSF leak?
When a skull fracture tears adjacent dura, creatining a communication between the subarachnoid space and the nose/sinuses/ear -can see presence of air within the subdural/subarachnoid/ventricular space on CT which indicates a dural tear
226
What are 2 clinical signs suggesting uncal herniation?
1. Unilateral 3rd nerve palsy 2. Contralateral hemiparesis \*\*\*Temporal lobe is shifting across the tentorial edge and pushing on the brainstem
227
What is the most common cause of primary subarachnoid hemorrhage?
Berry aneurysm of one of the major cerebral arteries in circle of willis
228
What are the guidelines for determination of brain death? -8 criteria -2 possible ancillary tests -rules for newborns 1 yo?
Requires a cause of coma sufficient to account for the loss of brain function should be established -in the setting of hypoxic-encephalopathic injury (ie. from cardiac arrest), exam must be delayed more than 24 hours post injury -in trauma patient with mechanical head injury, exam doesn't have to be delayed!! 1. 2 physicians must be present 2. The physicians must be qualified to do the assessment 3. Body temperature \> 34 (\>36 for newborns) 4. No confounding drug intoxication 5. No spontaneous movements, communication or interaction with the environment 6. No supraspinal response to externally applied stimuli 7. Absence of brainstem reflexes: i. pupillary light ii. oculocephalic (dolls eye maneuver) iii. oculovestibular (cold caloric stim) iv. corneal v. oropharyngeal (gag) vi. tracheal (cough) = tug on ETT 8. Apnea test: 10 min period of preoxygenation with 100% O2, take an art gas. Then turn off ventilator and watch for spontaneous breathing, repeat art gas and see if PaCO2 rises to \> 60. -CO2 has to increase by 20 mm Hg AND rise above 60 mm Hg AND pH has to be 1 yo: need two physicians but can perform the exam concurrently
229
What are the 3 main categories of etiologies of hydrocephalus?
1. Obstruction of CSF pathways: -Foramen of Monro obstruction: craniopharyngioma, germinoma, pituitary tumor, intraventricular tumor (ependymoma), tuberous sclerosis -Aqueduct of sylvius (cerebral aqueduct) obstruction: midbrain tumor, postinfectious -impaired flow from 4th ventricle to the foramen of magendie and two lateral foramina of luschka -dandy walker malformation -arnold chiari malformation 2. Overproduction of CSF: choroid plexus papilloma 3. Defective resorption of CSF (ie. communicating hydrocephalus): hypoplasia or destruction of arachnoid villi (absorbs CSF)
230
What is Parinaud syndrome?
Sunsetting eyes = dilation of the cerebral aqueduct compresses the surrounding periaqueductal vertical gaze centre = paresis of upward gaze -seen with CNS tumors or hydrocephalus
231
What are 2 most common organisms that infect VP shunts?
1. Staph epidermidis 2. Corynebacterium
232
What is the difference between neuronal degenerative disorders and leukodystrophy?
-Neuronal degenerative disorder: diseases affecting grey matter -Leukodystrophies: diseases affecting white matter
233
Which enzymatic disorders are most common causes of neurodegenerative dseases? (3)
1. Lysosomes 2. Mitochondria 3. Peroxisomes -any patient presenting with a degenerative neurologic condition should have leukocytes or skin fibroblasts harvested for measurement of lysosomal, peroxisomal, mitochondrial enzymes
234
How do you classify gray matter neuronal degeneration conditions? -what are the conditions in each class? (4 each)
Separate into disorders WITH or WITHOUT hepatosplenomegaly -With HSM: 1. Mucopolysaccharidoses (Hurler syndrome, Hunter syndrome, Sanfilippo syndrome) 2. Mucolipidosis 3. Niemann-Pick disease 4. Gaucher disease -Without HSM: 1. Tay-Sachs 2. Rett syndrome 3. Neuronal ceroid lipofuscinosis 4. Mitochondrial diseases: ie. MELAS
235
What are clinical features of mucopolysaccharidoses? (6) -cause? -examples?
Caused by defective lysosomal enzymes resulting in the accumulation of mucopolysaccharides 1. Dwarfism 2. HSM 3. Kyphoscoliosis 4. Coarse facies 5. Cardiac abnormalities 6. Corneal clouding -Examples of mucopolysaccharidoses: 1. Hurler syndrome (most severe) 2. Hunter Syndrome 3. Sanfilippo syndrome
236
What are the clinical features of Niemann-Pick disease? -cause?
Cause: deficiency of sphingomyelinase thus sphingomyelin accumulates in cells of the reticuloendothelial system (liver, spleen, lungs, bone marrow, brain) 1. Intellectual retardation/regression 2. Myoclonic seizures 3. HSM 4. Hypotonia 5. Retinal cherry red spots
237
What are clinical features of Tay-Sachs disease? -cause?
Cause: gangliosidosis caused by deficiency of hexosaminidase A = accumulation of GM2 ganglioside in cerebral gray matter and cerebellum -Normal until 6 months of age, then develop irritability, listlessness, hyperacusis, intellectual retardation and retinal cherry-red spot -overall: blindness, convulsions, spasticity, opisthotono
238
What are the clinical features of MELAS?
Mitochondrial myopathy Encephalopathy Lactic Acidosis Stroke like episodes
239
What are the prominent common clinical features of leukodystrophies? (6)
1. Spasticity 2. Ataxia 3. Optic atrophy 4. Peripheral neuopathy 5. Seizures 6. Dementia
240
What are examples of leukodystrophies? (3)
1. Metachromatic leukodystrophy: AR lipidosis caused by deficiency of arylsulfatase -demyelination of CNS/peripheral nervous system 2. Krabbe disease: AR lipiosis caused by deficiency of galactocerebrosidase 3. Adrenoleukodystrophy: X-linked with progressive central demyelination and adrenal cortical insufficiency -inability of peroxisome to degrade unbranced very long chain fatty acids -most common presentation = boys in early school years who develop subtle behaviour changes and intellectual deterioration, followed by cortical visual and auditory deficits and stiff gait
241
What are the clinical features of Friedreich ataxia? (6)
Manifests in early teenage years: 1. Ataxia/dysmetria 2. Dysarthria 3. Pes cavus/hammer toes 4. Diminished proprioception/vibration 5. Nystagmus 6. Hypertrophic cardiomyopathy \*\*\*think cerebellar/brainstem dysfunction, feet and heart
242
What are clinical features of ataxia-telangiectasia? -findings on lab investigations?
AR genetic disorder of DNA repair 1. Neurologic symptoms: ataxia, dystonia, chorea, swallowing difficulties, oculomotor apraxia (makes head movements to compensate for inability to generate saccadic eye movements), intellect is preserved, wheelchair bound by childhood 2. Telangiectasias: conjunctival, skin 3. Premature grey hair 4. Recurrent sinopulmonary infections \*\*\*Think: neuro, skin, immunological deficiency, gonadal dysgenesis Lab findings: high AFP, low IgA
243
What are the clinical features of Lesch-Nyhan syndrome? -treatment?
X-linked; deficiency of an enzyme that leads to excess uric acid 1. Psychomotor retardation 2. Spasticity 3. Severe self-mutilation 4. Gouty arthritis with renal calculi \*\*\*treatment: allopurinol to treat hyperuricemia and renal complications but there is no effective treatment for the neurologic disease
244
What are clinical features of Wilson disease? -lab finding? -treatment?
AR inborn error of copper metabolism 1. Neuro symptoms from copper deposition in the CNS: in teenage years, see dysarthria, dysphasia, drooling, fixed smile, tremor, emotional lability 2. Abnormal copper deposition in the liver = cirrhosis 3. Kayser-Fleischer rings from copper deposition in the cornea -lab finding: decreased serum ceruloplasmin -treatment: copper-chelating agent = oral penicillamine
245
What 2 CNS tumors occur commonly in neurofibromatosis type 1?
1. Optic nerve glioma 2. Astrocytomas
246
What tumors are seen in neurofibromatosis type 2? (3)
1. Schwannonmas: acoustic, cranial or spinal nerves 2. Meningiomas 3. Gliomas
247
What is schizencephaly?
Symmetrical abnormal bilateral clefts within the cerebral hemispheres that extend from the cortical surface to the ventricular cavity
248
What is lissencephaly?
Smooth brain with absence of sulcation
249
What is the classic triad of Dandy-Walker malformation?
1. Complete or partial agenesis of the cerebellar vermis 2. Cystic dilation of the 4th ventricle 3. Enlarged psoterior fossa
250
Which neurodegenerative conditions have retinal cherry-red spots? (4) -what causes the retinal cherry spots?
Retinal cherry spots: abnormal accumulation of lipids in ganglion cells surrounding the center of a normal retinal macula 1. Niemann-Pick disease (has HSM) 2. Tay-Sachs (GM2 gangliosidosis) (does NOT have HSM) 3. Mucolipidoses 4. Sandhoff disease (gangliosidosis type 2)
251
What is the enzyme deficiency seen in Tay-Sachs disease?
Deficiency of hexosaminidase A
252
How do you confirm a diagnosis for malignant hyperthermia?
Caffeine contracture test: muscle biopsy tissue specimen is exposed to caffeine = muscle spasm is diagnostic for malignant hyperthermia
253
What is ADEM?
Acute disseminated encephalomyelitis -initial inflammatory, demyelinating event with multifocal neurological deficits accompanied by encephalopathy
254
What are possible triggers for ADEM?
1. Preceding infection: viruses, mycoplasma 2. Postvaccination \*\*\*Essentially have CNS autoantigen production and antibody formation
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What are the clinical features of ADEM? (6) -findings on MRI -usual age of presentation
1. Lethargy 2. Fever 3. Headache 4. Vomiting 5. Seizures 6. HALLMARK = ENCEPHALOPATHY (confusion, irritability, coma) -findings on MRI: large, multifocal enhancement in white and grey matter of cerebrum, cerebellum and brainstem -usual age of presentation
256
What is the treatment for ADEM?
IV high dose steroids to decrease inflammation, consider IVIG or plasmapheresis
257
Which metabolic condition is associated with poor growth, developmental delay, and risk of STROKES/THROMBOEMBOLIC EVENTS?
Homocystinuria
258
A baby presents to yuo with a prominent occiput, broad forehead, absent anterior fontanelle and a long and narrow head. Otherwise normal. What is your diagnosis?
Primary craniosynostosis of the sagittal suture leading to scaphocephaly = long and narrow skull = boat shaped head!
259
A patient presents to the ED with sudden onset of headache with fall to the floor. On exam, he has a left central facial weakness, left hemiparesis with conjugate ocular deviation to the right. What is the diagnosis?
Stroke! Abrupt onset of hemisyndrome with eyes looking AWAY from the paralyzed side indicates acute stroke.
260
What is the difference between the weakness seen in myotonic dystrophy versus other muscular dystrophies?
Myotonic dystrophy weakness and wasting is DISTAL first (will progress to proximal) whereas other myopathiesare proximal muscle weakness -in myotonic dystrophy, will see weakness in hand movement
261
What associated features on exam can be seen in myotonic dystrophy? (4)
1. Ptosis 2. Baldness 3. Cataracts 4. Hypogonadism
262
A patient presents with signs of meningitis, pleiocytosis in CSF with high protein and low glucose and a CT scan with contrast enhancement of the basal cisterns. What is your diagnosis?
TB meningitis -Exudate in the basal cisterns is classic -can also see tuberculomas, ringed lucencies, infarction
263
What is the classic finding on pathology of an astrocytoma?
Rosenthal fibers
264
What is the enzyme deficiency seen in GM 1 Gangliosidoses? -clnical features?
Complete lack of acid Beta-galactosidase activity -clinical features: CNS degeneration, HSM, macroglossia, coarse facial features, cherry-red spots, gingival hyperplasia, edema of extremities
265
In which age group are night terrors most commonly seen?
Age 5-7 yo
266
What are the clinical features of PHACE syndrome?
1. Posterior fossa malformations 2. Hemangiomas 3. Arterial anomalies 4. Coarctation of the aorta 5. Eye abnormalities \*\*\*Consider in any child with a unilateral facial lesion and blidnness
267
What is Arnold-Chiari malformation?
Downward displacement of cerebellar tonsils through the foramen magnum -may cause hydrocephalus -4 types total
268
What is an AVM? -clinical features of unruptured AVM? -risk of rupture? -clinical features of ruptured AVM?
AVM = abnormal connection between arteries and veins (congenital) -clinical features of unruptured AVM: 1. Intracranial bruit heard through open fontanelle 2. High output cardiac failure due to abnormal shunting between arterial and venous systems 3. Local brain ischemia = focal neurological deficits, seizures, headaches Risk of rupture: 2% per year Clinical features of ruptured AVM: sudden, severe headache and loss of consciousness, with rising ICP due to intracranial hemorrhage with subsequent coma and death if no intervention
269
What is the most common ortho problem seen in NF-1?
Scoliosis
270
What is the inheritance pattern of neurofibromatosis-1?
Autosomal dominant
271
What is the underlying cause of trigoncephaly? -clinical features? -treatment?
Cranosynostosis of metopic suture -clinical features: pointed forehead, hypotelorism -treatment: craniostomy with removal of metopic suture
272
During what phase of sleep does neonatal sleep myoclonus occur in? -prognosis?
Non-REM sleep = bilateral rhythmic jerks involving upper and lower limbs -can be reproduced by slow rocking of the infant in a head to toe direction -no autonomic changes seen, occur ONLY in sleep, stop with awakening -this helps differentiate these from seizures -resolve spont at 2-3 mo age
273
At what time of the day does benign myoclonus of infancy usually occur? -age of onset? -prognosis? -how to differentiate between infantile spasms?
Benign nonepileptic infantile spasms = brief tonic contractions occur in clusters -USUALLY at mealtimes -first occur at 3-8 mo of age, then resolve spont at 2-3 yo -really cannot differentiate on history or physical exam between these and infantile spasms (REMEMBER YOUR LITTLE BABY FROM ED) and thus, need to refer to neuro asap and get EEG/MRI -if EEG and MRI are normal and baby is developmentally normal, then this is benign myoclonus of infancy.
274
What is the differential diagnosis of CN 7 palsy? -what is the diagnosis in a baby with just mouth drooping and other facial muscles are functioning well?
1. Idiopathic (Bell's Palsy) 2. Congenital (Mobius syndrome) 3. Traumatic - forceps delivery, LGA 4. Infectious - varicella, HSV, lyme disease 5. Other - cholestoetoma, tumors -diagnosis: congenital absence of the depressor angularis oris -sparing of the nasolabial fold
275
What are the two types of GM2 gangliosidoses?
1. Tay Sachs: hexosaminidase A deficiency 2. Sandhoff disease
276
What is the most common reason for surgical intervention in a child born with a myelomeningocele?
Hydrocephalus = needs surgical repair within a day or so after birth, often with a VP shunt too
277
What is the most common cause of spastic diplegia?
PVL
278
What is the first line treatment for acute migraine? -what about tension headache?
Migraine = NSAIDs Tension headache = acetaminophen
279
How can you differentiate between positional plagiocephaly vs. craniosynostosis?
In positional plagiocephaly, should have ipsilateral anterior displacement of the ear!!!
280
How do you differentiate post infectious cerebellitis from meningoencephalitis? (3) -what are 3 potential etiologic agents causing post infectious cerebellitis?
1. No fever 2. No altered LOC 3. No seizures 3 potential etiologic agents: 1. VZV 2. Coxsackie 3. Echovirus
281
What is the concern with use of valproic acid or carbamazapine during pregnancy?
Neural tube defects
282
What is the diagnostic criteria for migraine?
1. . At least 5 attacks PLUS 2. Headache lasts 1-72 hrs PLUS 3. Two of: a. Bilateral location b. pulsating quality c. moderate to severe intensity d. aggravated by physical activity PLUS 4. One of: a. nausea or vomiting b. photophobia or phonophobia
283
What are the criteria for a positive apnea test in diagnosis fo brain death? -when would ancillary testing be required?
1. CO2 has to increase by 20 mm Hg 2. CO2 has to rise ABOVE 60 mm Hg 3. pH has to be
284
Red flags for neurological disorder in newborn on prenatal history? (5)
1. Premature birth 2. Decreased fetal movement 3. Polyhydramnios due to impaired swallowing (weakness) 4. Trouble establishing feeding? 5. Resuscitation required after birth?
285
How can reflexes help you differentiate between muscle vs. nerve problem?
Nerve problem = reflexes will be completely absent -muscle problem = reflexes will be present or reduced
286
What investigation should be ordered after 1 unprovoked seizure? -what about 2nd unprovoked seizure?
After 1 unprovoked seizure: EEG!!!!! After 2 unprovoked seizures: MRI Head
287
What is one treatment you can start for breath holding spell?
Iron supplements
288
Which antiepileptic causes renal calculi? -which causes significant behavioural issues? -which causes gingival hyperplasia and coarsening of facies? -which causes stevens johnsons syndrome?
Bilateral renal calculi = topiramate Significant behavioural issues = keppra Gingival hyperplasia and coarsening of facies = phenytoin Stevens johnsons syndrome = lamotrigine
289
What are the health surveillance guidelines for neurofibromatosis type 1?
Yearly! 1. Check BP 2. Ophtho exams 3. MRI any suspected plexiform neurofibromas 4. Monitor growth: short stature, delayed puberty (have their own growth charts) 5. Developmental assessment/school support 6. Scoliosis exam 7. Vision screening/hearing
