Transcript ABIM_Neurology

Neurology Review
Dementia
• RECENT ADVANCES:
• Memantine Beneficial in Alzheimer’s
Disease
• Antipsychotic therapy and increased
mortality in Alzheimer’s Disease.
DSM-IV criteria for Dementia
• A. development of multiple Cognitive deficits
with both
– 1. Memory impairment
– 2. One or more of the following
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Aphasia
Apraxia
Agnosia
Disturbed executive functioning
• B. Significant impairment in social or
occupational functioning and represent a
significant decline from prior
• C. Not exclusively during a Delerium
NINCDS-ADRDA Criteria for
Alzheimer’s Disease
• 1. Dementia established by clinical examination
and standardized brief Mental Status exam and
confirmed by Neuropsychological tests
• 2. Deficits in two or more areas of cognition
• 3. Progressive worsening of memory and other
cognitive functions
• Onset between 40 and 90 years old
• Absence of other systemic or neurologic
disorder sufficient to account for progressive
cognitive defects
FDA approved Medications for AD
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Donepezil
– Mild to moderate
– Start at 5mg per day, up to 10mg, Titrate 4 – 6 weeks
– Nausea, Diarrhea, Abdo pain, sleep disturbance
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Rivastigmine
– Mild to moderate
– Start at 1.5mg bid, up to 3 – 6mg bid, Titrate 6 weeks
– N/V, anorexia, dizziness
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Galantamine
– Mild to moderate
– Start 4mg bid, up to 8 – 12mg bid, titrate 8 weeks
– N/V, Anorexia, weight loss, diarrhea
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Memantine
– Moderate to severe
– Start 5mg/d, up to 10mg bid, titrate 3 weeks
– Hallucinations, confusion, restlessness, anxiety, dizziness, headache, fatigue,
constipation
Alzheimer’s Disease: Key Points
• Normal neurologic exam except for characteristic broadbased cognitive and prominent recent memory
impairment
• Mild cognitive impairment is most likely a pre-demential
stage of AD
• Cholinergic augmentation with a centrally acting
cholinesterase inhibitor is standard therapy in
Alzheimer’s Disease
• Moderate to severe disease, memantine modestly
improves cognition and global function better than
cholinergic augmentation
• Vitamin E therapy may help slow progression of AD but
is not indicated in patients with mild cognitive impairment
or significant cerebrovascular disease.
Consensus Criteria for Frontotemporal Dementia
• 1. Insidious onset and gradual decline
• 2. Early decline in social interpersonal
conduct
• 3. Early impairment in regulation of
personal conduct
• Early emotional blunting
• Early loss of insight
Criteria of Probable Dementia with
Lewy Bodies
• 1. Persistent Memory impairment may not occur early
but is usually evident with progression. Deficits of
attention, frontal-subcortical skills, and visuospatial
ability may be particularly prominent
• 2. Two of the following core features
– a. Fluctuating cognition with pronounced variation in attention
and alertness
– Recurrent visual hallucinations that a typically well formed and
detailed
– Spontaneous motor features of parkinsonism
• 3. Supportive features include repeated falls, syncope,
neuroleptic sensitivity, delusions, other hallucinations,
REM behavior disorder
Other dementias Key Points
• Vascular dementia, Dementia with Lewy Bodies, and frontotemporal
dementia most common
• A clinical diagnosis of vascular dementia is established by history of
stroke risk factors, a stroke-like disease course, and/or findings on
imaging.
• Dementia with Lewy bodies is characterized by parkinsonism
repsonsive to dopaminergic therapy, visual hallucinations, and/or
fluctuating cognition
• Cholinergic augmentation (rivastigmine) may alleviate psychiatric
symptoms a/w dementia with Lewy bodies.
• Frontotemportal dementia presents with early executive and
personality change and pronounced or asymmetric frontal (and
temporal) atrophy on brain imaging
• Creutzfeldt-Jakob disease should be suspected in patient with
dementia a/w myoclonus that progresses over weeks to months
Clinical criteria for probable
Creutzfeldt-Jakob Disease
• 1. Rapidly progressive dementia
• 2. EEG with periodic sharp waves or
elevated 14-3-3 protein in CSF
• 3. Two of the following
– Myoclonus
– Visual or cerebellar signs
– Pyramidal or extrapyramidal motor signs
– Akinetic mutism
Headache and Migraine
• Primary vs secondary headache
• Migraine
– (Trigeminal-vascular system)
• Tension-type
• Cluster (trigeminal autonomic cephalgias)
• Other primary headaches
Migraine-specific acute Rx
• Ergot Derivatives
– DHE
• Triptans
– Sumatriptan
– Rizatriptan
– Zolmitriptan
– Others (Frovatriptan has long half-life)
Nonspecific Rx for headaches
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ASA
Acetominophen
Fiorinal/fioricet
Midrin
Cafergot
NSAIDs
Antiemetics
Migraine rescue
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Avoid narcotics
Ativan
Lidocaine
Magnesium
Depakote
Atypical antipsychotics
Solumedrol
Antiemetics IV
Hydroxyzine
Migraine prophylaxis
• Beta-blockers
• Calcium channel blockers
• Anticonvulsants
– Topiramate
– Valproic Acid
– Others
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Tricyclics
Sansert (not available)
Periactin
Coenzyme Q10
Vitamin B2
Magnesium
Headache Keypoints
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Migraine headaches originate in the brainstem and higher brain structures
that cause pain coming from inflamed cerebral blood vessels
Acute migraine Rx includes specific therapy with triptans or ergots
Triptans are contraindicated in patients with significant coronary risk factors
or a history of coronary disease
Rx of migraine should be administered as early as possible in the attack to
ensure the greates efficacy using the lowest dose of therapy
Prophylactic migraine Rx is indicated in patients who experience more than
2 days with headache per week.
Proper sleep hygiene may be the most effective migraine prophylaxis
Consumption of foods containing tyramine, nitrates, dairy products, and
xanthines may trigger migraine is some people
Menstrual migraine prophylaxis includes administration of low-dose
estrogen therapy during menstruation, continuous estrogen therapy
increased during menstruation, or oral magnesium
Medication overuse Keypoints
• Patients who use pharmacologic therapy
for headache more than 2 days per week
are at risk for medication overuse
headache
• Management of medication oversuse
headache includes migraine prophylaxis
and complete withdrawal of the medication
of overuse.
Other headache Keypoints
• Immobility increases cluster headache pain,
whereas increased movement exacerbates
migraine
• Patients with cluster headache may benefit from
high dose corticosteroid therapy administer for 2
– 4 weeks with taper over 2 – 4 weeks
• Primary sleep disorder should be excluded in all
patients with chronic headache syndromes.
Headache eval - Keypoints
• LP should be performed in patients with
headache only after CT or MRI excludes
mass lesion or hydrocephalus
• Temporal artery Bx is the study of choice
for Dx of GCA
• High-dose corticosteroid therapy is
indicated in GCA
• If untreated, GCA may cause blindness
More headache Keypoints
• Idiopathic intracranial hypertension
(pseudotumor cerebri) may present with
disabling headaches and has potential risk for
blindness
• Patients with tirgeminal Neuralgia may benefit
from therapy with anticonvulsants and baclofen
• Surgical decompression of the trigeminal
ganglion may be beneficial in refractory
trigeminal neuralgia
Movement Disorders
• Recent Advance: Long term efficacy of
deep-brain stimulation in Parkinson’s
Disease
Classification of Parkinsonism
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Primary Parkinsonism
Secondary Parkinsonism
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Parkinsonism-Plus Syndromes
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Medications
Hydrocephalus
Infections
Metabolic
Neoplastic
Psychogenic
Toxin
Traumatic
Vascular
CBD
Dementia syndromes
Multiple System Atrophy
PSP
Hereditary and Degenerative Parkinsonism
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Familial basal ganglionic calcification
FTD linked to Chromosome 17
HD
Wilson’s Disease
Fragile X premutation carriers
others
Rx of Parkinson’s Disease
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Amantadine
Apomorphine*
Carbidopa-levodopa
Entacapone (COMT inhibitor, in Stalevo)
Dopamine agonists
MAO-B inhibitors (Rasagaline)
Anticholinergics (Trihexyphenidyl)
Treating PD
• If no functional impairment: Neuroprotective Rx
– Antioxidants, Co-10, Azilect, Glutamate Antagonists,
creatine
• If tremor predominant: Amantadine or
anticholinergic
• If not tremor dominant and < 70: Dopamine
agonist, Sinemet, Amantadine, Azilect
• > 70 years old; Sinemet, MAO inhibitors
PD Keypoints
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In 75% of patients, rest tremor is first motor manifestation
Rigidity in PD may manifest as either cogwheeling or lead-pipe rigidity
Management of patients >70 with new Dx involves not inducing or
exacerbating cognitive impairment
L-dopa is the most potent agent currently available to control symptoms in
all age groups
Carbidopa with L-dopa decreases likelihood of peripheral dopaminergic
effects
Early dopamine agonist Rx is recommended in patient with PD < 70, early
Rx with Sinemet is recommend >70
Anticholinergic agents may help with tremor and rigidity but are typically
indicated only for younger patients without signs of dementia
Surgical procedure of choice is deep-brain stimulation of the subthalamic
nucleus
Surgery may benefit younger patients who respond well to Sinemet but
continue to experience significant periods of medication inefficiency and
dyskinesias despite optimal treatment.
Movement Disorders misc
• Drug induced parkinsonism
– Antiemetics etc
• Dystonias
• Essential Tremor
– Propranolol, Mysoline, Neurontin, Topiramate
• Huntington’s Disease
• Restless Leg Syndrome
– Check for Iron deficiency
Multiple Sclerosis
• Most common cause of non-traumatic
neurologic disability in young adults
• Signs/Symptoms
• Diagnosis
• Course
• DDX
– Cervical spondylosis, myelopathies, DM,
neurosarcoid, SLE, Sjogren’s, Vit B12 deficiency
• NMO
MS cont’d
• Rx exacerbations
• Disease modifying Therapies
– Interferons
– Glatiramer
– Natalizumab (blocks migration of
inflammatory cells, a/w PML
– Mitoxantrone
– Other immunosuppressants
• Symptomatic Rx
MS keypoints
• On MRI, the presence of ovoid lesions perpendicular to the lateral
ventricles and corpus callosum are characteristic of MS
• Management of leg spaciticity a/w MS should involve PT for
stretching and pharmacologic Rx
• The decision to treat an exacerbation of neurologic deficit with
corticosteroids is determined by whether the patient’s function is
affected
• Plasma exchange may benefit patients with severe exacerbations of
MS that are refractory to steroids
• PT, OT, ST may be appropriate after severe MS exacerbations
• There is no therapy that convincingly slows degenerative processes
in MS or definitively provides neuroprotection.
• Treatment of primary progressive MS is limited to symptomatic Rx
Peripheral Neuropathies
• Recent advance: Muscle-specific Kinase
antibodies in Myasthenia Gravis
• Axonal vs Demyelinating
• Acquired vs hereditary
– Charcot-Marie-Tooth disease is most
common hereditary neuropathy
• Toxins
Neuropathies a/w pain
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Cryptogenic Sensorimotor neuropathy
Diabetic Neuropathy
Vasculitis
GBS
Radiculopathy/plexopathy
Alcoholic neuropathy
HIV sensorimotor Neuropathy
Syphilis
Heavy Metal toxicity
Amyloidosis
Fabry’s disease
Hereditary sensory/autonomic neuropathy
Peripheral Neuropathy eval
• Standard:
– CBC, Chemistries, SPEP/IFE, B12, glucose assessment, RPR, TFTs
• Optional:
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HIV, ESR, ANA, RF, SS-A, SS-B
Anti-Hu
Genetic studies
Lyme titre
Heavy metals – 24 hour urine
Phytanic acid
• LP if suspecting CIDP or AIDP
• NCVs
• Sensory nerve Bx
– If vasculitis suspected
Symptomatic Rx of Neuropathic
pain
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TCAs
AEDs
Lidocaine Patch
Capsaicin cream
Acupuncture
Transcutaneous nerve Stim
Tramadol
Guillain-Barre
• Rapidily progressive, immune-mediated demyelinating
polyneuropathy
• Up to 75% a/w preceding infection, immunization, or
surgical procedure
– EBV, CMV, Campylobacter, Lyme, Hepatitis, HIV
• Weakness, pain, paresthesias, autonomic symptoms,
facial weakness, ophthalmoparesis, respiratory failure
(25%)
• 2 – 4 weeks
• Respiratory monitoring – FVCs etc
• EMG
• Rx: IVIG or Plasmapheresis
Polyneuropathy keypoints
• Asymmetric involvement should raise suspicion for MND,
radiculopathies, plexopathies, compressive neuropathies, or
mononeuritis multiplex
• Viral illness, immunization, or surgery may precede GBS
• DDX of neuropathy with Mental Status change should include B12,
thiamine, or niacin deficiency
• Immunosuppresive Rx indicated for CIDP
• NCV may be helpful to determine Axonoal vs demyelinating process
• Treatment of idiopathic polyneuropathy generally limited to pain Rx
• Hospitalize and do frequent respiratory monitoring for suspected
GBS
• Rx with IVIG or plasmapheresis GBS patients who are unable to
ambulate independently and have impaired respiratory functions or
rapidly progressive weakness
• Oral immunosuppressive rx for CIDP; IVIG or plasmapheresis
indicated for severe or refractory CIDP
Amyotrophic Lateral Sclerosis
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ALS – both UMN and LMN
Primary Lateral Sclerosis – UMN
Primary Bulbar palsy – Brain stem
Progressive muscular Atrophy – LMN
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~2/100,000 incidence.
Slight male predominance
95% sporadic
Mean survival 2 – 5yrs
Rx of ALS
• Riluzole is approved for ALS (very modest
effect)
• PEG
• Noninvasive PP ventilation with Bilevel
positive airway pressure may prolong
survival and improve quality of life
• Symtomatic Rx for spasticity, emotional
lability, muscle cramping, and drooling
may maintain dignity and quality of life
Myasthenia Gravis
• Antibodies against the AChR
• Characterized by fatigable weakness
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Ocular with diplopis, ptosis
Bulbar with dysarthria, dysphagia
Proximal extremity
Neck with head drop
Respiratory with dyspnea
• Dx: repetitive Nerve Stim, Tensilon (not
availbable) or SF-EMG may help
• Rx: Mestinon, immune Rx
– May initially get worse on Prednisone
Medications to avoid in MG
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Calcium channel blockers
Beta-blockers
Quinine
Quinidine
Procainamide
Lidocaine
Aminoglycosides
Polymyxin
Morphine
Barbiturates
Neuromuscular blocking agents
Magnesium
MG keypoints
• There is an increased incidence of thymic
abnormalities and thyroid disease in patients
with MG
• 85% of patients with generalized MG are AChR
antibody positive
• Mild cases may be treated with
acetylcholinesterase therapy (pyridostigmine
60mg tid or qid), whereas worse presentations
may benefit from immunosuppresive Rx
• IVIG or Plasmapheresis may help severe
weakness
Myoglobinuria
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Prolonged intensive exercise
Viral and bacterial infections
Drugs and toxins (EtOH!)
Neuroleptic Malignant syndrome
Heatstroke
Severe metabolic disturbance
Inflammatory myopathies (rare)
Limb-girdle muscular dystrophy
Metabolic Myopathies
– Ex) Myophosphorylase deficiency)
Myopathies presenting in
Adulthood
• Muscular dystrophies
• Inflammatory Myopathies
– Polymyositis, dermatomyositis, IB myositis, HIV
• Metabolic Myopathies
– Acid maltase deficiency, lipid storage disease, etc
• Mitochondrial Myopathies
• Endocrine Myopathies
• Toxic Myopathies
– EtOH, corticosteroids, etc
• Myotonic dystrophy
• Distal Myopathies
Myopathies- key points
• Myoglobinuria may manifest with exercise-induced weakness and
myalgias and cola-colored or red urine
• Many familial – family history
• Cardiac disease a/w myotonic dystrophy and some muscular
dystrophies
• FVC and Max inspiratory pressures monitoring
• CK most useful lab test
• CK elevated also in muscle trauma, viral conditions, seizures,
stenuous exercise, and some medications
• Benign elevated CK may occur in African American Population,
some muscular patients, and hereditary.
• Molecular genetic testing may avoid muscle BX
• CK and EMG are normal in corticosteroid induced myopathy
• Critical illness myopathy commonly occurs in setting of Rx with
corticosteroids and NM blockers
Brain tumors etc
• Temozolomide for GMB is new
• Meningiomas most common in peri- and post-menopausal women
• Radiographic and clinical observation usually OK for small,
asymptomatic meningiomas
• CT scan in meningiomas: extra-axial calcified mass with
homogeneous enhancement
• MRI more sensitive for meningiomas bu less reliable for showing
calcium
• Surgical resection recommended for symtomatic mengiomas
• Focal radiation for unresectable, recurrent, or anaplastic
meningiomas
• Most gliomas in adults are high grade and incurable
• Resection and XRT indicated for most high-grade gliomas, whereas
chemotherapy may benefit younger patients with good performance
status.
More tumor stuff
• Primary CNS lymphoma occurs infrequently in immunocompenent
patients, but is relatively common in immunocompromised patients
• Aggressive resection for primary CNS lymphoma is not indicated
• Chemotherapy usually followed by XRT is indicated for
immunocompetent patients with primary CNS lymphoma.
• Lung, breast, and melanoma are most common solid tumors to
metastasize to the brain
– Have high index of suspicison
• Rx: Steroids for vasogenic edema, XRT for multiple mets, surgery
for solitary met
• Paraneoplastic Syndromes:
– Limbic encephalitis, cerebellar degeneration, sensory neuronopathy,
opsoclonus-myoclonus, LEMS
– anti-neuronal antibodies
Epilepsy
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Partial vs Generalized Seizures
Localization related vs primary epilepsies
Optimize monotherapy
Surgery may be effective for medically
intractable localization-related epilepsy
• Medications
• Status Epilepticus
Stroke
• See separate presentation