Miscellaneous Disorders Flashcards
(119 cards)
1
Q
An autoimmune disorder resulting in damage to the neurons of the CNS
A
Multiple Sclerosis
2
Q
4 characteristics of Multiple Sclerosis
A
- chronic inflammation
- demyelination
- gliosis (plaques or scarring)
- neuronal loss
3
Q
cause hypothesis of MS
A
an environmental agent or event (eg, viral or bacterial infection, exposure to chemicals, lack of sun exposure) occurs in the presence of a genetic predisposition to immune dysfunction resulting in an autoimmune attack on the CNS neurons
4
Q
pathophys of MS
A
- Insult to immune system results in development of autoreactive lymphocytes (inflammatory T cells, B cells, and macrophages) that cross the BBB
- An inflammatory reaction occurs breaking down the myelin around the axon resulting in what is know as an MS “lesion”
- in some cases the axon is also damaged - An unsuccessful attempt at remyelination leads to a build up of rubbery or hardened plaques (sclerosis)
5
Q
MS is MC in who?
A
- Females > males - 2:1¹
- Onset - varies based upon subtypes - between 20-40 years of age
- RRMS - average age 28-31
- PPMS - average age 40
- onset later in men than women - Highest incidence in Caucasians and those in the northern US
6
Q
risk factors of MS
A
- genetic predisposition - 7-fold increase in risk if 1st degree relative has MS
- low vitamin D
- Epstein-Barr virus (EBV) exposure
- cigarette smoking
7
Q
presentation of MS
A
- “attacks” or “exacerbations” and reflect area in neuronal damage has occured
- Onset:** abrupt or insidious**
-
asx to severe
- asx may have abnml exam or evidence on imaging - sx are “separated in time and space”
- Episodes occur months or years apart and affect different anatomic locations - sx may be worsened by increase in body temp (Uhthoff Phenomenon)
-
Sensory sx
- Paresthesias - burning, tingling, “foot’s asleep”
- Hypesthesia - decreased sensation, numbness
- Unpleasant sensation - sensation of swelling, wrapped tightly, band-like, wet or raw
- Pain - neuropathic and musculoskeletal in nature
- Lhermitte’s sx - shock-like sensation radiating down back of legs (rarely arms) -
Optic Neuritis - MC unilateral but may be bilateral
- blurred vision
- pain with EOM movement
- central field visual disturbance often follows pain - diminished visual acuity, dimness, or decreased color perception
- Relative Afferent Pupillary Defect (RAPD)
- Optic disc - may be normal or pale (atrophy often follows ON) -
Motor sx
- weakness - worsened by exercise, facial weakness may resemble Bell’s palsy, diplopia if EOM affected
- spasticity (due to UMN lesions)
- hyperreflexia
- (+) Babinski signs
- intention tremor
- dysarthria (slurred speech) -
CN involvement
- Trigeminal neuralgia - CN V
same s/s as idiopathic TN but often bilateral, before age 50
- Facial myokymia - CN VII - involuntary twitching
- Glossopharyngeal neuralgia -
Bladder dysfunction
- detrusor hyperreflexia
- detrusor sphincter dyssynergia - Bowel changes: constipation or fecal urgency/incontinence
-
Sexual dysfunction
- Male: decreased libido/sensation, ED, premature ejacultation, orgasmic dysfunction
- Females: reduced libido, vaginal sensation and vagnial lubrication; anorgasmia, vaginismus/dyspareunia - Cognitive dysfunction - MC mild
- Depression (50% of pts)
-
Fatigue (90% of patients)
- most often what leads to work-related disability
- exacerbated by elevated temperatures, depression, sleep disturbances - Vertigo
- Paroxysmal symptoms (timing)
8
Q
intense electric shock-like pain in the posterior pharynx, tongue or ear triggered by swallowing or without warning
A
Glossopharyngeal neuralgia
9
Q
Neurological symptoms lasting 10-120 seconds and occuring 5-40 x/d
Thought to be a result of spontaneous discharges from neurons at the edge of demyelinated plaques
A
Paroxysmal symptoms (timing)
10
Q
Paroxysmal symptoms (timing) are precipitated by ?
A
hyperventilation or movement
11
Q
Paroxysmal symptoms (timing) consist of?
A
Lhermitte symptoms, tonic contractions, dysarthria, ataxia, sensory disturbances
Often self-limiting after weeks to months
12
Q
types of MS
A
- Clinically Isolated Syndrome (CIS)
- Relapsing-remitting MS (RRMS)
- Secondary progressive MS (SPMS)
- Primary progressive MS (PPMS)
13
Q
represents the first attack of MS
must last for at least 24 hours, is characteristic of multiple sclerosis but does not yet meet the criteria for a diagnosis of MS
what type of MS
A
Clinically isolated syndrome (CIS)
14
Q
90% of cases
discrete attacks of neurological dysfunction that evolves over days-wks (relapse), followed by partial or complete recovery over wks to months (remission)
between attacks patients are neurologically stable
what type of MS
A
Relapsing-remitting MS (RRMS)
15
Q
starts as RRMS, at some point in the course of the disease a deterioration in function occurs unassociated with the acute attacks
what type of MS
A
Secondary progressive MS (SPMS)
16
Q
10% of cases
a steady decline in function from disease onset
lacks the relapse-remission characteristics
what type of MS
A
Primary progressive MS (PPMS)
17
Q
DX criteria for MS
A
-
2 or more episodes of sx and 2 or more signs that reflect pathology in different areas anatomically
- lesions on MRI can act as the 2nd sign if necessary - sx lasting > 24 hrs and must be separated by at least a month in recurrence
- MRI brain with gadolinium contrast
- Acute MS lesions: larger with ill-defined margins. (lasts appx 1 month)
- Chronic lesions: smaller with sharper margins
18
Q
a measurement of electrical activity in the brain in response to afferent or efferent stimulation
A
Evoked Potentials
19
Q
different types of Evoked Potentials
A
afferent - visual, auditory, touch
efferent - motor
20
Q
what work-up is indicated in MS asx pts?
A
Evoked Potentials
most effective in assessment of clinically uninvolved pathways
21
Q
what makes a (+) EP when testing for MS?
A
a marked delay in latency of a specific stimulation
diagnostic in an asx patient
22
Q
CSF analysis indication
A
Indicated in patients with CIS or an atypical presentation (e.g. MRI is nondiagnostic)
23
Q
CSF analysis reveals
Oligoclonal bands (OGB) found
Increased levels of intrathecal synthesized IgG
Mildly elevated WBC (< 75 cells/μL)
CSF protein is normal - mildly elevated
what is the dx?
A
MS
24
Q
immunoglobulins that represent the antibodies causing MS disease
A
Oligoclonal bands (OGB)
may be absent at the onset of MS
the number of bands may increase with time
25
what Atypical presentations and red flags should lead to consideration of other possible diagnoses
1. sx localized to the posterior fossa¹, craniocervical junction², or spinal cord³
1. patient is <15 or >60 years of age
1. clinical course is progressive from onset
1. patient has never experienced visual, sensory, or bladder sx
1. diagnostic findings (e.g., MRI, CSF, or EPs) are atypical
26
initial labs for MS
usually normal in MS - used to narrow down or rule out ddx
ESR , serum B12 level, antinuclear antibodies (ANA), treponemal antibody, Lyme titer
27
indication for acute therapy in MS
CIS, acute exacerbations
First ensure exacerbation isn’t due to increase in body temperature
28
acute therapy for MS
1. **_Glucocorticoids are mainstay_**
- no benefit for improving long-term disability or reducing the risk of subsequent attacks
- IV or oral methylprednisolone, 1000 mg/d for 3-7 days with or without a taper
2. **Plasma exchange** (5-7 exchanges every other day for 14 days)
- Removing pt plasma and replacing it with donor plasma or albumin
- Consider in pts _with fulminant attacks unresponsive to glucocorticoids_
- High cost, little EBM
29
goal in Disease Modifying Therapy for MS
reduce the frequency of clinical relapses and evolution of new lesions
30
before disease modifying therapy, what must you screen for?
screen for immunity to Hepatitis A,B,C and VZV
31
BBW of disease modifying therapy
risk of **progressive multifocal leukoencephalopathy (PML)**
an opportunistic viral infection (John Cunningham [JC] virus) of the brain that usually leads to death or severe disability
32
what antibodies to check before starting DMT for MS
JC antibodies
patients who are seronegative are less likely to develop PML
33
which monoclonal antibody is indicated for all forms of MS
ocrelizumab (Ocrevus) - infusion q6m
34
what are the oral DMT therapies for MS
* Fumarates
* Sphingosine 1-phosphate receptor (S1PR) modulators (-*mod*)
35
what are the two platform injecton DMT therapies for MS
* Glatiramer Acetate (Copaxone/Glatopa)
* Interferon β
36
what are 1st, 2nd, and 3rd line for MS tx?
1. monoclonal
2. Oral therapies
3. platform injection
37
T/F there are off-label and natural tx for MS
T
38
ataxia/tremor tx in MS
* Clonazepam, propranolol, primidone
* Thalamotomy and deep-brain stimulation - mixed results when utilized
39
Spasticity and spasms tx in MS
* Avoid triggers: infections, fecal impactions, bed sores
* PT, regular exercise, and stretching
* Baclofen oral or intrathecal pump if severe
* Other muscle relaxants: diazepam (Valium), tizanidine (Zanaflex), cyclobenzaprine (Flexeril)
40
weakness tx in MS
K+ channel blockers - dalfampridine (Ampyra) - indicated when LE weakness interferes with ambulation
40
pain tx in MS
1. Anticonvulsants - carbamazepine (Tegretol), gabapentin (Neurontin), pregabalin (Lyrica)
2. TCA’s - amitriptyline (Elavil), nortriptyline (Pamelor), desipramine (Norpramin)
3. Comprehensive pain-management program if above agents fail
41
bladder dysfunction tx in MS
1. Detrusor hyperreflexia
- Frequent voiding and decrease fluid intake in the evening
- oxybutynin (Detrol LA)
2. Detrusor/sphincter dyssynergia - terazosin (Hytrin)
3. Treat UTI’s promptly
- pt with PV residual urine volumes >200 mL are at high risk for recurrent infections
4. Frequency self-catheterization is often required
42
bowel dysfunction tx in MS
* constipation - increased water and fiber supplement; laxatives (if former doesn’t work)
* fecal incontinence - fiber supplement and antidiarrheal
43
depression tx in MS
SSRI, TCA’s, SNRI
44
fatigue tx in MS
tx options are all “off label”
1. methylphenidate (Ritalin), lisdexamfetamine (Vyvanse), Dextroamphetamine-amphetamine (Adderall)
1. modafinil (Provigil), armodafinil (Nuvigil)
1. amantadine
45
prognosis factors of MS
1. better prognosis
- ON or sensory symptoms at onset
- fewer than two relapses in the first year of illness
- minimal impairment after 5 years
2. worse prognosis
- truncal ataxia
- action tremor
- pyramidal symptoms
- progressive disease
46
pt ed for MS
1. Maintain a healthy lifestyle
- maintaining an optimistic outlook
- a healthy diet
- regular exercise without excessive overheating as tolerated - swimming is often well-tolerated because of the cooling effect of cold water
- correct vitamin D deficiency
47
An umbrella term used to describe a group of disorders that cause permanent, nonprogressive motor dysfunction affecting muscle tone, posture, and/or movement
Results from an insult to the developing brain during birth, delivery, or in the perinatal period
Cerebral Palsy (CP)
48
CP often occurs in the presence of a combination of risk factors
| Cerebral Palsy
Genetic abnormality, toxic or infectious etiology, or vascular insufficiency
Modifiable risks: maternal smoking, maternal heavy alcohol use, maternal obesity
49
MC risk factors for development of CP
| chart
**antenatal**
- premature and low birth wt
- intrauterine infections
- multiple gestation
- pregnancy complications
50
what protective factors are helpful against development of CP
obstetrical care
* magnesium sulfate
* abc
* corticosteroids
51
presentation of CP
* **Gross motor delay** in _1st year of life_
* Abnormal muscle tone - **MC hypotonia followed by spasticity**
* Definite **hand preference before 12 m** of age
* **Asymmetric crawling** or failure to crawl
* **Growth disturbances** (weight/height)
* **Hyperreflexia**
* Some cases - persistent primitive reflexes
* Others - toe walking, muscle spasms, involuntary movements (facial gestures), seizures, intellectual disability
52
classifications of CP
Based upon predominant impairment and location of disability
1. Spastic CP
1. Dyskinetic CP
1. Ataxic CP
53
CM CP (70-80%)
Characteristics: Increased tone, Hyperreflexia, Muscle contractures
which type of CP
Spastic Cerebral Palsy
54
1. Less common - 10 -15% of cases
2. Characteristics
- Involuntary movements
- Hyper- or hypotonia
- Trouble maintaining an upright position
- Variable degree of dysarthria
- Intellectual disability
which type of CP
Dyskinetic Cerebral Palsy
55
characteristics of Ataxic Cerebral Palsy
Least common < 5% of cases
* Impaired balance and coordination
* Speech typically is slow, jerky, and explosive
* Hypotonia
* Poor motor skills
* writing, typing or using scissors
* Difficulty with auditory and visual processing
56
confirming CP dx is best deferred until when due to postnatal brain development
after age 2
57
labs for CP
To rule out differential
* Thyroid function
* Ammonia levels (liver dysfunction or urea cycle defect)
* Lactate and pyruvate levels (metabolic disorders)
* Organic and amino acids (metabolic disorders)
* Chromosomal analysis (genetic disorders)
* CSF total protein (elevated in neonatal asphyxia)
58
imaging for CP
1. Cranial US
- MC for _unstable neonates who are unable to be transported for MRI/CT_
- Can identify hemorrhage, hydrocephalus and periventricular leukomalacia
- Abnormal findings need to be **followed up with MRI**
2. CT brain
- provides a better image > US
- can identify congenital malformations, intracranial hemorrhage, damage to the white matter near the ventricles
3. MRI brain
- best imaging modality after 2-3 wks of age
*Normal neuroimaging studies do not exclude CP, but may indicate a genetic or metabolic etiology*
59
Additional Diagnostic Testing for CP
* **EEG** - if concern for seizure
* **EMG/NCS** - used to r/o muscle or nerve disorder
* **Evoked potentials** - utilized if pt has auditory or visual dysfunction
60
management for CP
1. Therapy: physical, occupational, and speech
2. Spasticity
- Muscle relaxants, BZD’s, botulinum toxin
- Intrathecal baclofen pump
- Selective dorsal rhizotomy: surgical ablation of 70-90% of the dorsal (sensory) nerve roots, decreasing spasticity
3. Seizures - antiepileptic pharmacotherapy
4. Dystonia, chorea, athetosis
- Anticholinergics, dopaminergics, BZD’s
- Deep brain stimulation: electrodes are implanted into the brain which generate electrical impulses controlling movement
5. Orthopedic - eval for complications of scoliosis, contractures, joint dislocations (hip is MC)
6. Vision screening beginning in infancy
- Strabismus, refractive errors, and cataracts
7. Routine evaluation:
- Developmental surveillance at every well-child visit to assess for intellectual disability
- Speech and language evaluation
- Weight and nutrition
61
complications of CP
* Respiratory- risk of aspiration pneumonia, lung/bronchopulmonary dysplasia, bronchiolitis, asthma
* Gastrointestinal - reflux, constipation
* Skin - decubitus ulcers
62
An inflammatory disorder of a region of the body (most often an extremity) characterized by pain, swelling, limited ROM, vasomotor instability, skin changes and patchy bone demineralization.
Complex Regional Pain Syndrome
MC between 30-60 years of age
63
CRPS often follows ?
trauma: fracture, soft tissue injury or surgery
64
proposed mechanisms of CRPS
classic inflammation, neurogenic inflammation, and maladaptive changes in pain perception at the level of the CNS
65
acute presentation of CRPS
1. lasts appx 3 months
2. pain prevents use of limb
- neuropathic: burning, cutting, searing, pressure, tearing
- constant and disproportionate to the precipitant injury
- may be exacerbated by ambient factors - loud noises, stress, light touch, active or passive motion
3. swelling, erythema and edema of the extremity with dependance, hyperhidrosis, skin cool to touch
4. bone demineralization of the affected limb due to a lack of use
66
subacute presentation of CRPS
lasts for up to 9 months
persistent severe pain and fixed edema
cyanosis or pallor
dry atrophic skin
atrophy of the subcutaneous tissue
joint fibrosis - stiffness and limited use
further bony demineralization
67
chronic presentation of CRPS
* continues for 1 year after disease onset
* symptoms can last for years before abating or may be permanent
* pain is variable
* edema resolves
* skin is dry, pale, cool and shiny - flexion and extension creases become absent
* joint fibrosis persists leading to loss of function and stiffness
* bone demineralization become osteoporosis
68
criteria for CRPS dx
budapest criteria
1. continuing pain disproportionate to any inciting event
2. at least 1 sx in three of the four cateogries
- sensory - hyperesthesia and/or allodynia
- vasomotor - temp asymmetry and/or skin color changes and/or skin color asymmetry
- sudomotor/edema - edema or sweating changs and/or sweating asymmetry
- motor-tropic - decreased ROM and/or motor dysfunction and/or trophic changes
3. at least 1 sign in two or more of the following:
- sensory
- vasomotor
- sudomotor/edema
- motor/tropic
4. no other dx that better explains s/s
69
work-up for CRPS
1. **Plain radiograph** - _demineralization_ begins at the ends of the bones and progresses medially to involve the entire bone
2. **Bone scintigraphy (bone scan)** - _increased radiotracer uptake_ in areas of demineralization
- assesses bone metabolism in patient with active bone resorption
70
management for CRPS
1. **_PT and OT as soon as dx is made - 1st line tx_**
2. **Psychosocial and behavioral therapy**
- identify psychological factors contributing to pain
- treat any underlying mental illness
- cognitive behavioral therapy for pts with chronic CRPS
3. Pain management
- Start with **NSAIDs** (ibuprofen/naproxen)
- **Add neuropathic** pain management - gabapentin (Neurontin), pregabalin (Lyrica) or TCA
- **Topicals**: lidocaine or capsaicin
- **Bisphosphonates**: if evidence of abnormal uptake on bone scan
- Alternatives: (less favorable due to higher risk vs benefit ratio)
--- ketamine - lower than normal anesthetic doses can help with pain
--- calcitonin - may reduce pain by reducing bone resorption
--- glucocorticoids - very weak evidence of improvement in _only acute and subacute_
--- alpha-adrenergic antagonists and agonists - may reduce sympathetically maintained pain
71
indications for referral in CRPS
progressive symptoms and signs of CRPS
unsatisfactory response to the initial measures
72
interventional options in CRPS
* trigger point injections
* sympathetic nerve blocks
* spinal cord stimulation or dorsal root ganglia (DRG) stimulation
73
pt ed for CRPS
**explain the long term benefits of PT and OT to improve compliance **
* pt will experience an increase in pain with therapy
* remind them of the long term goal of regaining use of the affected limb
74
prognosis for CRPS
1. Uncertain and highly variable
1. Most patients report **some degree of prolonged disability**
1. **Recurrence is common**: 10-30% - Seen most frequently in younger patients
75
A fatal neurodegenerative disease of the lower and upper motor neurons characterized by progressive loss of motor function
Motor neuron degeneration and death with gliosis replacing lost neurons leading to retrograde axonal loss
Amyotrophic Lateral Sclerosis (ALS)
76
definition “amyotrophic”
atrophy of the muscle fibers
77
“lateral sclerosis”
definition
changes seen in the lateral columns of the spinal cord where the UMN degenerate and are replaced by fibrous astrocytes (gliosis)
78
pathophys of ALS
1. **Impaired astrocyte and microglia** release toxins
1. Impaired astrocyte = increased glutamate at the synaptic cleft = **increased uptake of Ca+**
1. **Mitochondrial dysfunction** inside neuron inhibits Ca removal. Excessive Ca = neurodegeneration via **oxidative stress**
1. **Mutant proteins** form intracellular aggregates worsening oxidative stress and turn into **neurofilaments** which results in neuronal death
79
most ALS are caused how?
sporadic
80
RF for ALS
* risk increased with age - peaks in mid 70’s
* family hx
* smoking - increasing evidence to support this
81
presentation of ALS
1. sx are very slow and progressive and will reflect the body segment of the affected UMN lesions
2. **Extremity dysfunction** (cervical, thoracic, or lumbosacral - _MC initial sx_)
- Tripping, stumbling, trouble running
- Foot or wrist drop
- Reduced finger dexterity, stiff, cramping, weakness
3. **Bulbar dysfunction**
- Slurred speech, hoarseness, decreased volume of speech, nasal dysphonia, _drooling_
- Aspiration or choking during meals
- Emotional lability, depression
- Involuntary laughing and/or crying (Pseudobulbar Affect Syndrome)
4. S/S - damage to both UMN & LMN
- **UMN lesions** - Babinski, hyperreflexia, spasticity, hypertonia, clasp-knife rigidity¹, pronator drift
- **LMN lesions** - muscle fasciculation, hypotonia, hyporeflexia
muscle fibrillation (not visible to human eye - seen on EMG)
5. Generalized weakness
- most often starts in the extremities
- gait abnormalities
82
how to dx ALS/additional work-up
**Diagnosis is clinical**
- Electromyography - _features of acute and chronic denervation and reinnervation_; rules out peripheral nerve disease
- All labs and imaging will be normal
83
DMT for ALS
* Riluzole
* Edaravone (IV or ORS)
* Sodium phenylbutyrate-taurursodiol
* Tofersen
84
MOA of Riluzole
not fully understood
inhibits glutamate release
85
which DMT is the only medication that has shown efficacy in extending life in ALS patients
Riluzole
86
a free radical scavenger that reduces oxidative stress
Slows the functional deterioration in some patients
best results if started early in course of disease
which DMT for ALS?
Edaravone (Radicava IV or ORS)
87
dual action in reducing neuronal cell death
reduces stress response
increases threshold for cellular apoptosis
Slows the rate of functional deterioration
which DMT for ALS
Sodium phenylbutyrate-taurursodiol (Relyvrio)
88
MOA of tofersen
* binds to the SOD1 mRNA, resulting in degradation and prevention of SOD1 protein synthesis
* Outcome: Reduces progression of disease
* for patients with a mutation in the superoxide dismutase-1 (SOD1) gene
89
management for ALS
1. Smoking cessation
1. Refer to ALS center for a multidisciplinary approach - GI, pulmonology, psych, PT/OT/ST, respiratory therapy
1. Clinical trials - ALS.org - Experimental Therapy - UTD
1. Refer to hospice when needed
89
symptomatic therapy for ALS
1. Spasticity - baclofen, tizanidine (Zanaflex)
2. Drooling
- Anticholinergics (amitriptyline, scopolamine)
- Sympathomimetics (pseudoephedrine)
- Salivary gland irradiation
- Botulinum toxin type B - risky as the toxin could spread to bulbar or respiratory muscles
3. Depression - SSRI
4. Ventilatory support
- BiPAP at night in patients with sleep disturbances or nocturnal hypoventilation
- Invasive ventilatory support, requiring tracheostomy, is often needed
5. Nutritional support
- speech therapy and nutritionist if difficulties with swallowing/appetite
- percutaneous endoscopic gastrostomy (PEG) tube placement may be needed
6. Physical/Occupational therapy
- maintain a low impact exercise regimen to maintain ROM and tone, prevent contractures
90
MCC of death in ALS
aspiration pneumonia
Median survival is 3 years from clinical onset of weakness
91
An acute condition resulting in global cerebral dysfunction in the absence of primary structural brain disease
Toxic-Metabolic Encephalopathy
92
pathophys of Toxic-Metabolic Encephalopathy
Dysfunction of the ascending reticular activating system and/or its projections to the cerebral cortex, leading to impairment of arousal and/or awareness
93
RF for Toxic-Metabolic Encephalopathy
* ICU placement
* Older patients
* Underlying dementia
94
presentation of Toxic-Metabolic Encephalopathy
1. **Cognitive dysfunction** ranging from confusion to delirium or coma
- disturbed sleep-wake cycle, decreased alertness, hypervigilance, hallucinations, sensory misperceptions, impaired memory, and disorientation
2. **Seizures**
3. Exaggerated physiologic **tremor**
4. **_Asterixis_** - flapping tremor
5. **Myoclonus** - sudden, nonrhythmic, gross muscle twitching, particularly involving the face and proximal muscles
6. **(+) Babinski, brisk DTR**
95
causes of Toxic-Metabolic Encephalopathy and which is MC
1. **Sepsis - MCC**
1. Hepatic encephalopathy
1. Uremic encephalopathy
1. Severe electrolyte abnormalities
- hyponatremia - most often due to SIADH
- hypernatremia
- hypo-, hypercalcemia
- hypomagnesemia
- hypophosphatemia
2. Hypoglycemia
1. Hyperosmolar Hyperglycemic State (HHS)
1. Diabetic Ketoacidosis (DKA)
1. Wernicke encephalopathy
1. Hypoxic-ischemic encephalopathy
1. Post-transplantation encephalopathy
96
work-up for Toxic-Metabolic Encephalopathy
1. **MRI / CT scan**
- indicated to r/o ddx when focal signs are present on physical examination or when subdural hematoma is suggested by the history
2. **EEG**
- confirms global cerebral dysfunction and excludes subclinical seizures
3. **Lab studies**
- CBC, CMP
- PT / PTT
- ABG, lactic acid
- Toxicology
- Blood and CSF cultures
- TSH, Vit B12, serum cortisol, ammonia
97
management for Toxic-Metabolic Encephalopathy
Identify and treat underlying condition
Remove any drugs that could exacerbate delirium
98
A genetic disorder characterized by tumor formation on nerve tissue that results from a mutation or deletion of tumor suppressor genes
Neurofibromatosis (NF)
99
T/F Neurofibromatosis (NF) are MC malignant
F - most tumors are benign, but can be malignant
100
3 types of Neurofibromatosis (NF)
1. Neurofibromatosis Type 1 (von Recklinghausen Disease)
1. Neurofibromatosis Type 2
1. Schwannomatosis
101
presentation of Neurofibromatosis Type 1
1. Appears in **childhood**, most often by age 10
2. **strong FHx** - Autosomal dominant or de novo
3. **Cafe au lait spots** - _> 6 spots_ = strong indication for NF1
4. **Freckling of the axilla or groin** - appears by age 3-5
5. **Lisch nodules**
6. **Neurofibromas** - MC _not painful/tender_
- MC _on or under the skin_, but can grow deep inside the body
7. Plexiform neurofibroma
- tumor formation on a _nerve plexus, can lead to disfigurement_
8. Bone - **scoliosis or bowing of the lower legs**
- diminished bone mineral density, abnormal bone growth
9. Optic nerve (optic glioma)
- **visual disturbances, proptosis** (tumor pushes the eye outward)
- **compression on pituitary gland** - hormonal problems - abnormal growth, weight gain or loss, endocrine dysfunction , early puberty
10. Learning disability - mild; *ADHD* common
11. Larger than normal head size - increased brain volume
12. Short stature
13. Elevated BP - d/t renal artery stenosis or pheochromocytoma
102
Gold-tan-brown dome-shaped gelatinous masses on the surface of the iris.
Lisch nodules
103
Criteria for NF type 1
Requires at least **2 of the 7 NIH criteria**
* Many of these signs do not appear until later childhood or adolescence.
* Confirming the diagnosis often is delayed despite a suspicion of NF1.
104
work-up for NF1
Utilized to assess for complications of NF1
1. Optic glioma - MRI brain
2. Pheochromocytoma - MRI/CT abdomenl Urine fractionated metanephrines and creatinine
3. Renal Artery Stenosis (RAS) - US, MRA of the abdomen
4. Bone disease - X-rays if clinical findings indicate bony defect
105
management for NF1
1. No specific treatment - treat individual manifestations as they arise
1. Referral to a multidisciplinary clinic experience in NF management
1. Annual assessment
- Monitor for new lesions and progression of current lesions
- Monitor BP
- Monitor growth and development
- Skeletal changes
- Learning development
- Annual eye exams
2. Genetic counseling - All patients and family members
106
surgery indications for NF1
pain, bleeding, interference with function, disfigurement
Consult plastic surgeon if located in area of cosmetic concern
107
surgeries for NF1
1. Consult plastic surgeon if located in area of cosmetic concern
2. Plexiform neurofibromas
- complete resection usually results in residual functional deficits
- debulking or partial resection may be needed for cosmetic or functional purposes
- consult plastics
3. Pheochromocytoma
- treat appropriately
- consult surgeon experienced in management
4. RAS
- refer to vascular surgery
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complications for NF1
**Malignant peripheral nerve sheath tumors** (MPNSTs) and **neurosarcomas** are common (lifetime risk of 10%).
- Often arise from large plexiform neurofibromas or extensive peripheral nerve lesions.
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red flags of NF1 complications
* significant and persistent pain within the lesion
* transition of lesion from soft to hard
* rapid growth of a nodule
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what are NF2?
A condition characterized by **tumors of the CNS and PNS**
- less prominent cutaneous manifestations than NF1
- 50% of cases result from new mutation - FHxif often negative
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presentation of NF2
1. sx onset usually **late teen and early adult years**
1. MC lesion - **benign, slow-growing tumors in of the vestibulocochlear nerve **
- AKA: vestibular schwannomas, acoustic neuroma
- gradual hearing loss, tinnitus
- ataxia
- headaches
2. Other lesions: meningioma, schwannoma (nerve sheath), glioma, neurofibroma, cataracts
- numbness and weakness in the arms or legs
- pain
- balance difficulties
- vision problems or the development of cataracts - may be seen on exam long before vestibular tumor formation
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dx criteria of NF2
1. Clinical - NF2 Criteria
1. Genetic testing
1. MRI brain/spine
- _brain_ - indicated as a **screening tool** in high risk individuals for **acoustic neuroma**
- _spine_ - any pt with **motor or sensory changes suggestive of a spinal cord lesion**
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management for NF2
1. Referral to NF clinic
- Annual auditory evaluation
- Annual ophthalmic exams
- Annual neurologic exam
2. Genetic counseling for patient and family members
3. Tumor management
- surgical resection (standard of care)
- chemo or radiation therapy may be used
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A rare condition resulting in multiple painful noncutaneous schwannomas without vestibular involvement
Most often occurs due to an acquired genetic defect after birth
Schwannomatosis
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presentation of Schwannomatosis
1. Often affects people after age 20
2. focal pain
- neuropathic and nociceptive features
--- neuropathic: hot, cold, cutting, crushing, burning
--- nociceptive: sharp, aching, or throbbing
- can occur anywhere and may be disabling
3. focal numbness and weakness
4. muscle atrophy
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work-up for Schwannomatosis
1. Genetic testing - may or may not identify genetic defect
2. MRI with + without contrast
- **brain** - r/o _CN VIII_ involvement
- **spine** - look for spinal cord involvement and r/o spinal cord impingement
- **focused peripheral nerve** - assess a specific location
-** whole body MRI** may be used to determine extent of disease
*Confirmed (definite) Dx ONLY*
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management of Schwannomatosis
1. Refer to NF clinic
2. tx is mostly symptomatic
- neuropathic pain management - gabapentin or pregabalin
- NSAIDs or short acting opiates for breakthrough pain
- add on agents
--- TCA’s - amitriptyline (Elavil)
--- SNRI - duloxetine (Cymbalta)
--- antiepileptics - topiramate (Topamax), carbamazepine (Tegretol)
--- short acting opiates for PRN severe pain
3. Nonpharmacologic therapy - no EMB to support treatment but may work
- mediation, yoga, hypnosis, biofeedback, acupuncture
4. Surgical resection - last resort
