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NEUROLOGY REVIEW
The bare bones of the thing
Cerebrovascular Disease
Neurodegenerative Conditions
Epilepsy
Demyelinating Disease
Neuropathies
Headaches
Neuromuscular Conditions
Cerebrovascular Disease
• Risk factors: Age, Family Hx, HTN,
Cholesterol, Diabetes, Heart Disease
(esp Afib, cardiomyopathy, atrial
thrombus, PFO), tobacco use,
excessive etoh use, hypercoagulable
states (cardiolipin syndrome, CA, antithrombin 3 deficiency, prot C and prot S
deficiency)
Ischemic vs Hemorrhagic
• Ischemic strokes of
sudden onset or
stuttering in onset
• Deficits worse at
onset with gradual
improvement
• Most common
type(85%)
• Hemorrhagic
strokes of sudden
onset
• Deficits worsen with
time
• Headache is
common
• Additional etiologies:
AVM, aneurysm,
amyloid angiopathy
Thrombotic vs Embolic
• Clinically, impossible to differentiate
• Most strokes are thrombotic (?80%)
• If potential source is identified (Carotid
stenosis, Afib, atrial thrombis,
cardiomyopathy, endocarditis, PFO,
aortic arch plaque, dissection) then
assume embolism. Otherwise, assume
intracranial thrombosis.
Left Hemisphere
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Right hemiparesis, hemisensory deficit
Aphasia if cortical location
Hyper-reflexia on right, Babinski on right
Initially flaccid tone with eventual
spasticity on right
Right Hemisphere
• Often silent or less pronounced
symptoms due to the dominance of the
left hemisphere
• Left hemiparesis, hemisensory deficit
• Anosognosia
• Hyper-reflexia on left with left Babinski
• Initially flaccid with eventual spasticity
on left
Occipital infarcts
• Left or right hemi-visual field loss
• Headache common
• Patient often misinterprets that one eye
doesn’t work. The examiner needs to discern
the truth by checking visual fields
Cerebellar infarcts
• Objectively: Ataxia, dysdiadachokinesis,
tremor, dysarthria, nystagmus
• Subjectively: Dizziness, nausea,
clumsiness
• Higher risk of hemorrhagic
transformation compared to other brain
areas
Brainstem Infarcts
• Cranial nerve signs: diplopia, facial
numbness, facial weakness, ptosis,
pupil irregularities, dysphagia,
asymmetric palate or tongue,
• Crossed motor or sensory deficits, or
even biparesis or quadraparesis
Transient Ischemic Attacks
• Three minutes or less. This is a meaningless
distinction. The event is still a stroke.
• Most significant is Amaurosis Fugax.
“Fleeting Blindness” may represent embolic
event from carotid stenosis
• Any TIA is a harbinger of another stroke in
the near future (15% chance within a month)
Workup
• MRI brain is preferable. CT’s are quick
• Carotid Duplex. MRA or CT angiogram
if dissection is suspected
• TTE or TEE
• EKG/Holter
• Hypercoagulation blood work if
indicated
Emergent Treatment
• Anti-platelet medication at onset
(except, of course, in hemorrhage)
• Anti-coagulation if embolism from Afib,
atrial thrombus, or cardiomyopathy, or
dissection is determined
• tPA if available within three hours of
onset.
Prevention
• Anti-platelet medication in almost all cases
• Anti-coagulation only in Afib, cardiomyopathy,
atrial thrombus, “shaggy aorta syndrome”
• Carotid endarterectomy if ipsilateral stenosis
greater than 70%
• PFO closure
• Treatment of underlying risk factors
Neurodegenerative Conditions
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Alzheimer’s Disease
Parkinson’s Disease
Huntington’s Disease
Progressive Supranuclear Palsy
Cerebellar Degeneration
Alzheimer’s Disease
• Estimated 50% of people age 85 years
• Familial if parent had disease in early to
mid 50’s
• Risk factors: loose association to past
head injuries, inverse association to IQ
and education level
AD Pathology
• Neurofibrilary tangles, neuritic plaques
• Generalized brain atrophy as disease
progresses, but especially in temporal
lobes
• Reduction in acetylcholine system
AD symptoms/signs
• Progressive “short term” memory
deficits, i.e. inability to form new
memories.
• Progressive aphasia
• Personality change
• Progressive deficits in ADL’s - Apraxia
AD Workup
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Brain imaging
B12 level, TSH
Mini Mental Status exam
Clock Drawing
AD continued
• The leading cause of dementia in the
USA is Alzheimers.
• The second leading cause is multiple
strokes
• The third cause is a combination of the
two above.
AD Treatment
• Acetylcholine esterase inhibitors Aricept, Exelon, Razadyne
• Glutamate inhibitor - Namenda
• These drugs only slow the progression
of the disease, they do not lessen the
deficits
• In this disease, you treat the family
perhaps more than the patient
Parkinson’s Disease
• Very common - estimated one in one
hundred between ages 60 and 70 years
• Tends to be sporadic
• Rate of disease progression is very
variable
PD Pathology
• Progressive degeneration of pigmented
dopamine producing cells in the
substantia nigra, i.e. nuclei in the midbrain
• Degeneration begins at birth.
• Symptoms appear when degeneration
reaches 80%
PD Symptoms/Signs
• Tremor - Resting. Often begins
unilaterally in extremities. Can involve
the jaw and tongue
• Rigidity - increased tone in the extremity
muscles. Cogwheeling if superimposed
tremor. Stooped posture
• Akinesia (bradykinesia)
• Postural Instability
PD Symptom/Signs continued
• Drooling, constipation, micrographia,
low volume stuttering speech, dementia,
reduced facial expression, reduced
eyeblink rate
PD Treatment
• Neuroprotective agents: Vitamin E, CoEnzyme Q10
• Dopamine agonists: Requip, Mirapex, Permax. More
useful early on when there are more dopaminergic
cells still functioning
• Anti-cholinergics especially for tremor
• Dopamine replacement: Sinemet
(carbidopa/levadopa). Gold standard treatment (high
risk of adverse effects at five years) - Less is Best
• Deep Brain Stimulation
Huntington’s Disease
• Autosomal Dominant disorder.
• Easily diagnosed via blood test that detects the
genetic defect, i.e. CAG repeat sequence - the longer
the sequence, the earlier onset and more severe the
symptoms
• Symptoms usually manifest in young adulthood
HD Clinical triad
• Chorea - involuntary, writhing or quick
movments of face, limbs, trunk
• Psychiatric disease - usually depression
and can occur before other deficits
• Dementia - usually occurs later
HD Treatment
• Is a progressive disease. Life
expectancy average 19 years
• No known treatment, except to treat the
depression when needed or to reduce
the chorea with dopamine blockers.
Dementia is resistant to treatment
• Again, treat the family
Progressive Supranuclear
Palsy
• Usual onset 6th to 7th decade
• Sporadic
• Pathology - degeneration of brain stem
nuclei in midbrain “and above” to the
basal ganglia
• Often mistaken for Parkinson’s Disease
because of the bradykinetic
appearance of the patient
PSP Continued
• Hallmark Sign: impaired voluntary vertical
eye movements
• Also, axial more than appendicular rigidity,
grimacing, drooling, dysarthria
• Prominent early symptom: Falling
especially going down steps (due to
impaired vertical eye movements)
PSP continued
• Treatment - none
• This is another disease where the
treatment is directed more to the family
than the patient
Cerebellar Degeneration
• Autosomal recessive types tend to
occur early adulthood
• Autosomal dominant types tend to occur
later life
• Both are slowly progressive and similar
in deficits
CD continued
• Progressive ataxia, dysarthria, irregular
tremor in extremities and trunk
(titubation), dysphagia, nystagmus
• Dementia is subtle and generally not
significant
Epilepsy
• A seizure is a single event due to an
abnormal discharge of a group of
cerebral neurons resulting in a
multifarious array of behaviors and/or
cognitive experiences
• There are many etiologies for seizures trauma, hypoxia, drugs, fever, etc.
Epilepsy Continued
• Epilepsy is a disorder of the brain that
produces recurrent spontaneous, seizures.
• Two age peaks - childhood to young adult
and later life (age 55+)
• Younger group has 5-20%chance of
resolution and is often hereditary. Older
group has little to no chance of resolution and
is usually sporadic.
Types of seizures
• Simple Partial - motor, sensory, visual,
cognitive or emotive event (depending on
location of the electrical discharge) WITHOUT
change in consciousness
• Complex Partial - the above WITH change in
consciousness
• Generalized Tonic-Clonic Seizure
• Absence, Myoclonic, Atonic, Tonic, Clonic
seizures
Types of Epilepsy
• Partial Epilepsies (location specific) result in
simple partial, complex partial or secondarily
generalized tonic-clonic convulsions. An
abnormal electrical focus in the brain may be
due to scar, tumor, congenital malformation
• Primary Generalized Epilepsies result in
absense, myoclonic, tonic, clonic seizures or
tonic-clonic convulsions. No abnl focus is
found. Rather, the brain has lower seizure
threshold.
Epilepsy workup
• Obtain as complete a history as
possible
• EEG to determine type of Epilepsy
(recall EEG’s only 90+% sensitive)
• Brain imaging re possibility of mass,
stroke, etc.
• Select urine tox screen or blood studies
as indicated
Epilepsy Treatment
• Medication choice depends, in part, on
type of Epilepsy
• Primary Generalized Epilepsies respond
best to Depakote, Lamictal, Keppra and
Topamax. Avoid Tegretol.
• The Partial Epilepsies respond to all
medications
Epilepsy treatment continued
• The Generalized Epilepsies are usually more
successfully treated, whereas the Partial
epilepsies are more challenging.
• 70% of people are 100% controlled on
monotherapy. The remainder require
polypharmacy and may not have 100%
control
• Vagus Nerve Stimulation and lesionectomy or
corpus callosotomy are used in refractory
cases.
Epilepsy medication side
effects
• Depakote - spina bifida, weight gain,
tremor, hair loss
• Tegretol - hyponatremia
• Dilantin - gingivitis, hirsutism,
osteoporosis
• Topamax - renal calculi
• Phenobarbitol - sedation and cognitive
impairment
Epilepsy and pregnancy
• Overall risk to mom and baby is greater
if mom is untreated.
• Birth defect rate general population 2%
• Birth defect rate untreated epileptics 4%
• Birth defect rate treated epileptics 6%
• Supplemental folate, monitor drug
levels, mom considered “high risk”
Status Epilepticus
• Thirty minutes or more of continuous seizing
or recurrent seizures without recovery
between them.
• Is an emergency because of potential
neuronal damage due to high metabolic
activity and hypoxia.
• Rx: Benzo first followed by IV Fosphenytoin
and possibly IV phenobarbitol
CNS Demyelinating Disease
• Multiple Sclerosis is an auto-immune disease
affecting both the brain and spinal cord in
which myelin is attacked by anti-bodies. This
results in destruction of the myelin and if
severe can lead to axonal destruction and
ultimately neuronal death.
• “Sclerosis” refers to the calcified scarring
seen in multiple areas of the brain and/or
spinal cord at autopsy
Demyelinating Disease
continued
• If only the spinal cord is affected, the
condition is referred to as Transverse
Myelitis
• Once the brain is affected , the
condition is referred to as Multiple
Sclerosis
• It is a disease primarily of young women
MS - Course of the disease
• Relapsing-Remitting 70%
• Primary Progressive 10%
• Secondary Progressive - about 50% of
the R-R type at 15 years
• Monosymptomatic - ?10%
• Devic’s Disease - TM plus ON only 5%
MS Workup
• MRI showing multiple (at least nine) periventricular lesions typically perpendicular to
ventricles, some of which enhance
• Lumbar Puncture revealing oligoclonal bands,
myelin basic protein, elevated CSF/serum
IgG ratio
• Visual Evoked Potential
• Clinical criteria “dissemination in time and
space.” This is still the best way to diagnose
MS Symptoms/Signs
• Typical relapse is gradual onset (2d to 2w) of
a neurologic deficit, plateau (2w to 2m) and
gradual recovery
• Deficits include motor, sensory, balance,
visual (Optic Neuritis in particular), speech,
cognitive problems
• Fatigue, depression, dementia common and
long lasting
• Average 2 relapses per year
MS Treatment
• Steroids useful in shortening the
duration of a particular relapse and in
reducing its’ severity
• Immunomodulating medications useful
in reducing relapse rate, reducing
“lesion load” in the CNS, and ultimately
in reducing long term disability
MS Treatment continued
• Currently six options
• Beta seron - LFT elevations, flu-like
symptoms, leukopenia
• Avonex - as above but less problematic
• Rebif - very similar to Beta seron
• These three are all Interferons and suppress
B cell antibody production.Higher potency
interferons are more efficacious but carry
increased adverse effects.
MS Rx Continued
• Copaxone - subcutaneous necrosis.
Acts by suppressing B cell antibody
production and entrance to CNS
• Novantrone - cardiomyopathy and
leukemia. Unclear mechanism of action
• Tysabri - Progressive Multifocal
Leukoencephalopathy occurs in 1/3000
patients
• Two oral therapies just available.
Neuropathy
DAMN THERAPISTS
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D Diabetes
A Atherosclerosis
M Monoclonal gammopathies
N Nutritional
T Trauma
H Hereditary
E Endocrine
R Rheumatoid Arthritis
Etiologies continued
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A Amyloid
P Paraneoplastic syndromes
I Infectious, idiopathic
S Sarcoid
T Therapy
S Sjogren’s syndrome, SLE
Neuropathy continued
• Subjectively is a slowly progressive
anesthesia/paresthesia/dysesthesia
and/or weakness initially affecting the
distal lower extremities that can
eventually affect the upper extremities.
• Objectively it involves varying severity
of sensory deficit and/or weakness with
reduced or absent reflexes.
Neuropathy workup
• Nerve Conduction Velocity and Electro
Myography (EMG) to help delineate
type (axonal vs demyelinating) and
severity
• Select blood work as related to Damn
Therapists
• Rarely, nerve biopsy
Neuropathy - Guilliane-Barre
Syndrome
• GBS is a sub-acute (2d to 2w) onset of
sensory deficit and weakness initially in distal
lowers progressing to uppers. It is often periinfectious.
• Pathologically, it is thought to be an immune
mediated attack on the sensory, motor and
autonomic peripheral nerves and also the
nerve roots.
• Technically, known as an acute, inflammatory
demyelinating polyneuropathy
GBS continued
• This can result in cranial nerve deficits and
life threatening cardiac arhythmias and
diaphragmatic weakness
• Exam reveals sensory loss and weakness in
extremities,reflex loss, often facial weakness,
pupil irregularities and dyspnea.
• The patient has back pain due to nerve root
inflammation
GBS continued
• Time is of the essence.
• Plasmapheresis or IVIG is used to remove
the offending antibodies from the serum
• Treatment shortens the duration and severity
of the attack and can save the life of your
poor, innocent, woeful, unsuspecting patient.
• Unfortunately, there is a recurrent form of this
disease (CIDP) which is progressive.
Headache
What a PAIN!
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Migraine
Analgesic Overuse Syndrome (Rebound)
Cluster
Trigeminal Neuralgia
Temporal Arteritis
Pseudotumor Cerebri
CSF Leak (Low pressure) headache
Migraine
• Lifelong disorder, usually most
prominent in reproductive years
• Females more than males
• Usually hereditary
• The imaging study is done to make sure
it is not a “secondary headache”
(secondary to a brain tumor or ruptured
aneurysm, or intracranial hemorrhage)
Migraine symptoms
• The pathophysiology involves activation
of the Trigeminal-vascular system
resulting in a decrease in serotonin,
increase in substance P and other
neuropeptides. This then results in
either intracranial vasoconstriction,
extracranial vasodilation or both
Migraine continued
• Clinically, the manifestations fall on a wide
spectrum from mild HA to severe throbbing
pain with N/V, photo, phono and osmophobia,
lasting hours to days at a time and often
accompanied by the most sincere wish to die,
NOW! rather than endure another moment of
torture.
• 85% of migraineurs experience only the
extracranial vasodilation
• 15% experience also the intracranial
vasoconstriction
Migraine Aura
(This is the interesting part)
• The aura depends on which area of the brain
is affected by the oligemia/hypoxemia.
• Occipital lobe - scintillating scotomas, visual
field loss, metamorphopsia
• Temporal lobe - deja vue, jamais vue, altered
emotions
• Parietal lobe - hemiparesis/hemisensory
deficit
• Frontal lobe - disinhibition, confusion
• Global - stupor and coma
Migraine Rx
• Abortive - triptans act as serotonin
agonists and lead to vasoconstriction
(Imitrex, Maxalt, Zomig, Relpax, etc)
thus reducing the pain
• Preventive - tricyclics act as serotonin
agonists, some anti-convulsants act as
glutamate inhibitors and some BP meds
help prevent vasodilation
Analgesic Overuse Syndrome
AKA Rebound
• Occurs when pt takes more than three days
weekly of any combination of analgesics
• Typically, HA in the AM (when the analgesic has
worn off). Pt then continually titrates the use of
the medicine(s) throughout the day
• Drug potency increases over time (one Tylenol to
three Motrin to Vicodin to Percocet to ER visits
requiring morphine)
• Requires about 2-3 weeks to develop into Chronic
Daily Headache
• Treatment - Stop the analgesics. Relief usually in
10 to 14 days.
Cluster Headache
• Typically middle aged males who
smoke
• Unilateral retro-orbital pain with
lacrimation, nasal congestion, Horner’s
syndrome that builds up over 5-10
minutes and last 60-90 minutes.
• Clusters around the same time of day
and/or season
Cluster Rx
• Abortive - Imitrex injection and
prednisone taper
• Preventive - Verapamil, Lithium
Trigeminal Neuralgia
• Severe, piercing, short duration pain in
one or several unilateral branches of the
Trigeminal Nerve occurring multiple
times daily often triggered by touch,
chewing.
• Atypical TN – paresthesias rather than
pain.
• MRI brain needed to rule out MS, brain
stem tumor or ectopic vessel pressing
on the Trigeminal Nerve
Trigeminal neuralgia Rx
• Most anti-convulsants help. Baclofen, a
CNS muscle relaxant sometimes useful
• Surgical treatment in refractory cases,
i.e. decompression if ectopic vessel is
found, or permanent ablation of the
nerve branch(s) or intracranial
compression of the nerve
Pseudotumor Cerebri
• Idiopathic intracranial hypertension resulting
in headaches, transient visual obscurations
and tinnitus
• Exam reveals papilledema
• Typically in females, obese or pregnant
• Certain anti-biotics can induce it tetracycline, minocycline
• Work up: MRI brain to rule out real tumor,
MRV to rule out venous sinus thrombosis and
LP to document high opening pressure
Pseudotumor Rx
• Diamox used to reduce CSF production
rate
• Sometimes repeat LP’s are required
• Optic Nerve Sheath Decompression in
refractory cases
• Venous sinus stent if sinus clot is
discovered
Low Pressure Headache
• Commonly occurs in a post LP situation, but CSF
leaks can also occur both spontaneously and
sometimes after trivial trauma.
• Initial W/U is LP (if thought to be spontaneous)
• Additional work up is radionucleotide cisternogram
showing CSF leaks along spinal canal
• MRI spine with gadolinium sometimes helpful
• Rx Epidural blood patch sets up sterile inflammation
in dura, sealing the leaks.
Temporal Arteritis
• Nonspecific HA in anyone over 55 years.
• Can be associated with jaw pain while chewing,
visual loss in one eye.
• Pathologically, inflammation of temporal artery and
its’ branches (to masseter muscle or to optic nerve)
• Work up is biopsy (Giant cells and vessel
inflammation) and ESR 55+
• Treatment is long term steroids or
immunosuppressants
Neuromuscular Conditions
• Amyotrophic Lateral Sclerosis
• Myasthenia Gravis
ALS
• Progressive neurodegenerative condition confined to
the motor system. Pyramidal cells of cortical motor
strip to the anterior horn cells of spinal cord.
• Spares eye movements (?) but affects all other motor
functions: facial control, tongue, swallowing,
breathing, sphincter control, limb and trunk muscles
• 25% of patients alive at five years
• Rilutek, a glutamate inhibitor, prolongs life about 13
months
Myasthenia Gravis
• Autoimmune disorder affecting old men and
young women
• Blockade/destruction of post-synaptic
acetylcholine receptors on muscles
• Hallmark is fluctuating weakness in certain
muscle groups, typically brain stem (ptosis,
diplopia, dysarthria) but can be generalized
affecting breathing, limb and trunk muscles.
MG diagnostics
• Acetylcholine receptor antibody level.
Sensitivity only 80%
• Repetitive Nerve Stimulation shows
decremental response in the muscles.
• Exam reveals fluctuating signs in the
office and increasing weakness with
prolonged strength testing
MG continued
• CT chest to rule out thymoma (thought to be
the source of the antibody production)
• Rx 1-Thymectomy if residual thymus or
thymoma discovered 2-Mestinon
(acetylcholine esterase inhibitor) as
symptomatic treatment 3immunsuppressants such as prednisone,
Imuran or Cellcept
Summary
• Know your neuroanatomy
• Listen to your patient
• In an emergency “Don’t just do something.
Stand there.”
• Learn to trust your instincts
• Consult your colleagues when in doubt
• Read. Read. Read.