Cranial Nerve Reflexes:

Corneal

Lacrimation

Jaw Jerk

Pupillary

Gag

Corneal - V1, VII

Lacrimation - V1, VII

Jaw Jerk - V3, V3

Pupillary - II, III

Gag - IX, IX + X

A lesion of the medial longitudinal fasciculus (MLF), which connects the subnucleus of CN III governing the medial rectus with the contralateral nucleus of CN VI governing the lateral rectus.

Therefore, when looking lateral away from the side of the lesion, the contralateral eye abducts with nystagmus and the ipsilateral eye cannot adduct at all.

A classic sign of multiple sclerosis.

V - Jaw deviation towards the lesion

VII, UMN - contralateral lower face paralysis since upper face has dual innervation

VII, LMN - ipsilateral full face paralysis

Bell's palsy - lesion in facial nucleus (UMN) or facial nerve (LMN)

X - Uvula deviation away from lesion

XI - Dropped shoulder ipsilateral to lesion; weakness turning head contralateral to lesion

Dysarthria testing:

Ka - palatal elevation (CN X)

La - tongue movement (CN XII)

Ma - lip movement (CN VII)

Cerebellar dysfunction - increasing difficulty reaching target as you approach target

Parkinson's disease - trajectory starts off wobbly but calms down as finger approaches target

Essential tremor - finger goes all over the place

Complete paralysis due to ventral horn involvement

Hypalgesia (decreased pain sensitivity) below the lesion

Intact proprioception/vibratory sense

Seen with vascular lesions of the anterior spinal artery

Combined UMN and LMN symptoms

Bowel/bladder dysfunction since parasympathetics at S2-S4 are also lost

Seen in older patients with cervical spinal stenosis due to osteophyte formation

Osteophytes - bone spurs caused by arthritis

Center of cord more severely affected than periphery

Also caused by obstruction of central canal, causing CSF to build up in the syrinx and compress cord

LMN findings at level of lesion

Loss of pain + temperature in "cape-like" distribution if obstruction is in cervical spine

This is because first fibers affected will be those of the anterior white commissure, carrying pain + temperature

Proprioception is preserved

Hemisection of the cord

Ipsilateral UMN findings below the lesion

Contralateral pain + temperature loss a few levels below the lesion

Ipsilateral DCML loss below the lesion

Ipsilateral radicular sensory loss and LMN findings at the level of the lesion

Involvement of nerve root only

Decreased sensation to touch and pinprick

Weakness

Hyporeflexia

All in the affected dermatome only

Extradural - bone destruction, complete block on myelograph, radiculopathy followed by myelopathy, caused by bone tumors, abscesses, or trauma

Intradural, extramedullary - spinal cord pushed to one side, myelopathy affecting DCML and corticospinal tract, caused by neurofibroma or meningioma

Intradural, intramedullary - spinal cord widened, myelopathy affecting DCML first, then spinothalamic tract and ventral horn, caused by ependymoma or astrocytoma

Bed rest, analgesics, and muscle relaxants first, followed by weight reduction, physiotherapy, and exercise

Surgery - partial hemilaminectomy for disc degeneration

Excision of benign tumors

Removal of disc herniations

Abscesses - drain, then find organism and provide appropriate antibiotic

Steroids are effective for some tumors

Occurs due to progressive degeneration of the cartilaginous annulus and loss of fluid in the nucleus pulposus

Lumbar lordosis, weak abdominal muscles, smoking, obesity, surgical discectomy, and repeated stress are other predisposing factors

Disc first bulges posteriorly, pushing against posterior longitudinal ligament, causing low back pain that improves with bed rest and worsens on sitting or movement

If annulus is weak enough, nucleus pulposus may herniate through and compress the dural sac and nerve root, causing sciatica

L2-L4 - decreased sensation in anterior thigh down to the medial aspect of the shin

L5 - loss of sensation in 1st and 2nd toes

S1 - loss of ankle jerk reflex, loss of sensation along lateral foot

S2-S4 - Bowel/bladder dysfunction

Fractures - trauma or osteoporosis

Tumor/infection - age > 50, history of cancer, presence of lines, pain that worsens at night (musculoskeletal problems should get better when lying down + resting)

Cauda Equina - saddle anesthesia, lax sphincter, urinary incontinence/retention, weakness in the legs

UMN below the lesion

LMN at the level of the lesion

All sensory modalities lost below the lesion

Posterior Lateral Column Syndrome

aka Subacute Combined Degeneration

Loss of proprioception with preserved pain + temperature sensation

Ipsilateral UMN findings below the lesion

No LMN findings at the level of the lesion, since those are in the ventral horn and are preserved

Can be caused by B12/vitamin E deficiency

Loss of DCML

May "feel" weak, but muscle strength is normal when tested

Most commonly caused by Multiple Sclerosis

Normal reflexes/motor w/ significant sensory loss

May be somewhat asymmetric due to asymmetry of MS lesions

Sensory gait - Ataxic walk since feet can't feel the ground

UMN and LMN findings, but with intact bowel/bladder function

Only ALS does this

LMN weakness below the lesion

No UMN findings since all the UMNs are in the spinal cord itself

The nerves in the cauda equina are all peripheral nerves, so there is complete loss of sensation bilaterally

Looks like a hemisection, but without the UMN findings

Disc herniation

Trauma

Tumor

B12 deficiency

Folate deficiency

Copper deficiency

Excess Zinc can cause copper deficiency

Vitamin E deficiency

B12/vitamin E deficiency can cause subacute combined degeneration

HIV

Syphilis

HTLV-1

Fungal

TB

Numbness/unsteadiness

Absent/reduced deep tendon reflexes

Paresthesia - pins and needles

Dyesthesia - something feels uncomfortable

Hyperpathia - something that normally feels uncomfortable feels even more uncomfortable

Allodynia - something that normally doesn't cause pain is painful

Restless leg syndrome

Atrophy

Fasciculations

Wallerian degeneration - nerve is cut and degenerates beyond the trauma point; muscle atrophies due to loss of axon supply

Axonal degeneration - longest nerves affected first; usually a metabolic condition such as diabetes

Neuronopathy - disease of cell body so that the nerve dies

Segmental demyelination - underlying axon is fine, so no atrophy, but muscle is weak since electrical conduction is compromised and action potentials can't reliably get through

Symmetric degeneration of long nerves (stocking-glove syndrome)

Usually have sensory findings before motor

Probably due to a mixture of metabolic problems (free radicals) with vascular insult (ischemia)

Can also find autonomic symptoms

Infarction of proximal elements of the lumbosacral plexus

Generally unilateral

Proximal-to-distal weakness

Elevated CSF protein due to injury to nerve roots

Infarction of a single peripheral nerve

Need to distinguish diabetic cause of CN III infarct from a compressive cause

Diabetic cause will not have any pupillary symptoms since the autonomic nerves are separate from the CN and a CN infarct will not affect them

Compressive aneurysm will take out autonomics as well

Immune attack on myelin, triggered by e. coli or campylobacter infection

Onset over days to weeks

Ascending paralysis

Most common acquired demyelinating polyneuropathy

Risk increases with age

Predominantly affects motor neurons, but will also see CN and/or autonomic nerve findings

Albuminocytologic dissociation - high protein with few white cells in CSF -> distinguishes G-B from diseases with similar symptoms like polio or West Nile

Treat by removing antibodies, either through plasmapheresis or IV Ig

EMG + nerve conduction studies helpful in diagnosis

Type 1 - myelin degradation -> most common demyelinating polyneuropathy

Type 2 - axonal degradation

Type 1 is more severe, so if person has late onset, more likely to be type 2

Distal weakness and atrophy, musculoskeletal deformities (hammer toe and high arch)

Presynaptic NMJ disorder involving autoimmune antibodies against voltage-gated Ca2+ channels, preventing release of Ca2+

Proximal weakness and autonomic dysfunction

Sparing of extraocular muscles

Strength improves with repetitive contractions

Strong association with small cell lung cancer

Treated with immunosuppression if no underlying neoplasm is discovered

Botulinum toxin prevents release of synaptic vesicles containing ACh

Toxin-contaminated home-canned foods or toxin formation within wounds

Progressive, descending weakness

Equine antitoxin used in adults

Human botulism Ig can be given to children

Autoimmune antibodies against post-synaptic ACh receptors or Muscle-specific kinase (MuSK)

MuSK is important for normal clustering of ACh receptors during development

Characterized by fatigable weakness

Associated with thymus disorders

Tensilon test - after getting ACh-ase, pts should regain strength

Treatments: anticholinesterases (symptomatic), immunosuppression, IV Ig or plasmapheresis, or thymectomy

Involved in muscle energy storage - provides a rapidly available reservoir of ATP needed in excitation/contraction coupling

Highest concentrations found in muscles + heart

Also present in brain, so severe brain injuries will cause an elevated CPK

Elevated in myopathies as well as some neuropathies that cause loss of axons and subsequent muscle loss

Normal values are highest for black males and lowest for white females

Lab norms are based on white males

X-linked recessive

Produce no or completely afunctional dystrophin

Wheelchair-bound by age 13, death in mid-20s

Serum CK very elevated, even when still asymptomatic

Muscle biopsy - degeneration/necrosis of muscle fibers, increased CT/fat, increased variability in muscle fiber size, lack of dystrophin on immunostaining

Proximal-distal weakness

Gower's sign

Cardiac muscle weakness is cause of death

Very large calf muscles, filled with CT and fat

Scoliosis and lumbar lordosis common, along with a wide-based stance due to weakness of legs

Same as Duchenne, but less severe

Still some functional dystrophin is produced

Onset 5-15, death mid-40s

Important structural protein connecting actin to the cell membrane

Stabilizes the excitation/contraction process

Most mutations are deletions

Need to be regularly tested for cardiac symptoms

If enough normal X chromosomes are inactivated, can show some mild symptoms

Try to maintain function - ankle braces + steroids

Steroids are only helpful as long as they help maintain ambulance -> once wheelchair bound, side effects outweigh benefits

Regular pulmonary function tests and EKGs

Surgery for severe scoliosis or tendon contractures

Overnight positive airway may be needed

Myoblast transfer - injection of myoblasts capable of making dystrophin -> unreliable

Aminoglycosides - help cells ignore stop codons, which can help if pt has a mutation with a premature stop codon

PTC 124 - allows exon skipping, so cell might be able to skip over a deletion area and produce some truncated, partially functional dystrophin

Most common muscular dystrophy in adults

Distal-proximal weakness

Myotonia - delayed muscle relaxation

Cardiomyopathy + electrical conduction deficits

Cataracts, frontal balding, temporal wasting

Gene defect in chromosome 19 -> amplified CTG repeat

Anticipation

Congenital version results from maternal inheritance

Milder than type 1

Gene defect on chromosome 3

Proximal-distal weakness

Less risk of cardiac defects

Still get cataracts

Type 1 - autosomal dominant

Type 2 - autosomal recessive

Usually progresses slowly

Involves disorders of the non-dystrophin proteins

Autosomal dominant, involving a gene defect on chromosome 4

Facial + proximal weakness

Scapular winging on both sides, with one side worse than the other

Popeye's arms - disproportionate weakness of biceps and triceps

Occasionally some distal leg weakness

Age > 20, Females > males

No rash, lower risk of malignancy than dermatomyositis

Proximal + mild facial weakness

EMG identical to dermatomyositis, high CPK

Muscle biopsy - necrosis, endomysial inflammation, perivascular inflammation, but NO perifascicular atrophy

T-cell mediated attack on muscle

Treat with immunosuppression

Females > males, subacute onset

Proximal + facial weakness

Dark, purplish rash on face, neck, shoulders, and extensor surface of arms that is difficult to detect in people with darker skin

Periorbital erythematous edema

Cardiac complications - conduction defects, pericarditis

Interstitial lung disease

Subcutaneous calcifications - common in children and can be very painful in fingertips or toes

Increased risk of malignancy in adults

B-cell mediated attack on small vessels

High CPK

Characteristic muscle biopsy - perivascular + endomysial inflammation, perifascicular atrophy due to ischemia, necrosis

Slowly progressive weakness with distinctive pattern - distal upper, proximal lower

High CPK

Muscle biopsy - identical to polymyositis unless you happen to get an eosinophilic inclusion in the sample

Occasionally misdiagnosed as polymyositis, but it won't respond to treatment

No proven treatment exists

Metabolic myopathy involving a defect in glycogen metabolism

Causes a limb-girdle pattern of weakness

Is treatable with enzyme replacement, so make sure not to miss it

Involuntary, sustained muscle contractions, producing twisting or squeezing movements with abnormal postures

Stereotyped, repetitive movements

Writer's cramp, blepharospasm

Dopa-responsive - rare form

Childhood - typically progressive to general dystonia

Adult - typically remain localized, task-specific dystonia

Treated with anticholinergics or benzodiazepines or botox (blepharospasm)

Deep brain stimulation being investigated

Excessive, spontaneous, involuntary movements that are abrupt, arrhythmic, irregular, and flow randomly from one muscle or body part to another

Ballism - fast chorea - wild, flinging movements involving proximal musculature

Athetosis - slow chorea - sinuous movements of distal musculature

Hemiballism typically due to contralateral lesion of subthalamic nucleus -> can be self-limited

Infections can cause chorea due to autoantibodies

Pregnancy - an estrogen surge affecting the basal ganglia that usually goes away after delivery

Tardive dyskinesia - caused by antipsychotic medications, especially those that block dopamine

Repetitive, brief, rapid, unvoluntary, purposeless, stereotyped movements

Unvoluntary - can be suppressed, but there is a compulsion to perform the action and a sense of relief when the action is performed

Normal behaviors that are performed out of context

Treated with dopamine depletors and benzodiapines

Worsens with dopaminergics and stimulants

A type of tic

Diagnosis requires: presence of multiple motor tics, 1 or more vocal tics, younger than 21, and symptoms persisting for at least 1 year

Associated with behavioral problems like ADHD and OCD

Seems to just be a more severe version of tics, since families with Tourette's have family members without Tourette's who do have chronic or transient tic disorders

Rapid, shocklike, discrete, arrhythmic, and often repetitive muscle jerks

Movements may be randomly distributed, focal, multifocal, or generalized

Can be physiological -> hypnic jerks are myoclonus as you are falling asleep

Essential myoclonus can run in families

Heavy chain allows binding to a receptor on the presynaptic neuron

Toxin gets internalized and cleaved

Light chain blocks fusion of ACh vesicles with neuronal membrane, preventing release of ACh

Causes muscular weakness with peak effect 3 weeks after injection and lasting up to 6 months

Typically, get injections every 3 months

Cervical dystonia - inject directly into muscles that are spasming

Blepharospasm - inject subcutaneously

Side effects are very localized and related to muscle weakness

Autosomal recessive, age of onset > 20, fatal unless treated

Defect in copper metabolism -> copper accumulates in liver, then spreads to other organs

Can present with cirrhosis, dystonia, or behavioral changes

K-F rings - copper-colored rings around the iris, especially at the top and bottom

A possibility for anyone under 50 with a movement disorder

Treated with copper chelation, liver transplant, diet management, treatment of symptoms, and drugs that decrease copper absorption in the GI tract

Family history often positive - can be autosomal dominant or recessive

Dentate nucleus lesion will cause permanent ataxia

Damage to Purkinje cells will also cause ataxia -> transient since Purkinje cells can recover

Climbing fibers from inferior olivary nucleus bypass granular layer and filter out irrelevant information -> excitatory and stimulate Purkinje cells, which are inhibitory

Glutamic acid decarboxylase - limiting reaction in synthesis of GABA, so presence indicates GABA neurons

Mercury + alcohol damage Purkinje cells

Fibers from the pons and spinal cord stimulate the cerebellar cortex

Cortex transmits to dentate nucleus which transmits to the thalamus

The dentate nucleus also inhibits the inferior olivary nucleus

The inferior olivary nucleus uses its own inhibitory fibers on the Purkinje cells

A lesion in the middle of the pons will look very similar to cerebellar ataxia, but will also have motor symptoms since the corticospinal tract also runs through this region of the pons

Cerebellar module = cortex, dentate, and inferior olivary nucleus

The dentate nucleus is the major output station of the cerebellum

Bradykinesia

Rigidity

Resting tremor - reduced with motion

Disease progression is slow, with major changes occurring over years

Tremor is asymmetric and responds very well to dopaminergic medications

Diagnosis based on exam/history

Glucocerebrosidase

Alpha synuclein

Tau

Ubiquitin Carboxy-terminal hydrolase L1 (UCH L1)

Parkin - Juvenile PD

These proteins are involved with mitochondrial function and power generation

Genes load the gun, Environment pulls the trigger

Age - the only definitive risk factor

Mean age of onset = 55-60

Toxins - MPTP (very toxic to DA neurons in substantia nigra), well water, pesticides, herbicides

Infection - post-encephalitis

Cigarette smoking

Male predominance

Ibuprofen (NSAIDs in general) may be protective

Nigrostriatal degeneration, particularly in the substantia nigra pars compacta

Will start at brainstem and move up, so can see other symptoms well before classic signs -> hypoosmia, constipation, bladder disorder, sleep disorder, depression, and movement during REM sleep -> premotor Lewy Body dysfunction

Intraneuronal cytoplasmic inclusions called Lewy Bodies

Rate model - subthalamic nucleus is excessively active

Focused excitation/Surround inhibition model - basal ganglia has several output channels, and for any given movement, the desired movement (muscle groups) is amplified by an excitatory pathway while other movements are suppressed by inhibitory pathways

Function of the basal ganglia - scaling of movement (velocity + amplitude), focusing of movement, learning motor sequences

Levodopa

Dopamine Agonists - delays onset of motor complications, but more side effects than L-Dopa, so only used in juvenile PD

Exercise - only thing that has consistently been shown to slow disease progression

Need vigorous exercise to see benefits

Causes regeneration of nerve connections (synapses) and nerve cells that allows greater retention of dopaminergic cells and less severe symptoms later on

Multiple System Atrophy - MRI looks abnormal (hypo + hyperactivity in pons that makes MRI look like a hot-cross bun)

Progressive supranuclear palsy - additional symptoms (neck rigidity, lack of postural reflexes, frequent falls, difficulty looking downwards, speech abnormalities develop early (2-5 years) rather than late (10-20 years), and MRI shows significant brainstem atrophy (penguin or hummingbird sign)

Essential tremor - just the tremor with no other symptoms, usually tremor is symmetric rather than asymmetric in PD, and tremor generally worsens with movement rather than improves

Autosomal Dominant

Onset 35-40 years, although a juvenile form exists

MRI - enlarged ventricles with progressive flattening of caudate as you lose neurons and get replacement with glial cells

Loss of basal ganglia, especially caudate and putamen, due to degeneration of GABA + ACh neurons

Early on - hyperkinetic - subtle hyperactivity with slow, fine finger movements (chorea), head movement/blinking, tend to break fixation - can't focus on one target for long

Later - hyperkinetic - difficulty maintaining tongue extension, lots of hyperactive, involuntary movements, dysphagia and difficulty swallowing, hyperreflexia

Very late - hypokinetic - body becomes very stiff

Depression is extremely common

Degeneration of medium spiny neurons in the striatum

Indirect pathway (inhibition of inhibitory interneurons) is hit first -> disinhibition of ventral thalamus causes hyperkinetic symptoms

Goes from cortex -> putamen -> GP externus -> subthalamic nucleus -> GP internus -> SN pars reticulata -> thalamus -> cortex

Direct pathway lost later - return of inhibition to ventral thalamus and hypo/bradykinetic state

Goes from cortex -> putamen -> GP internus -> thalamus -> cortex

Involves a CAG repeat on chromosome 4

Normal people have < 26 repeats

When number of repeats gets > 36-40, develop Huntington's

Decreased penetrance in people with 26-36 repeats

People with 21-30 repeats may be asymptomatic, but their children will be at greater risk for HD

As number of repeats increases, age of onset decreases

Juvenile HD = > 60 repeats

Anticipation is seen, especially in paternal transmission

Neuroleptics - DOPA antagonists

Helpful early on and causes weight gain as side effect, which is useful since patients are often hypermetabolic AND have trouble swallowing, so need all the calories they get

Tetra-HD - approved for treatment of chorea in HD patients -> side effects include depression + difficulty swallowing

Creatine - may show some slowing of progression

With fewer neurons/boutons, there are fewer reuptake sites so DA stays in synaptic clefts longer

Increased synthesis/release of DA in each remaining neuron

Increased DA receptors in the postsynaptic neurons

D2 receptor agonist

Half-life 3-6 hours

In many cases, recommended dose is ineffective or poorly tolerated

Frequently combined with L-dopa to cut dose -> increases basal level of activity in basal ganglia

Side effects: anorexia, nausea/vomiting, confusion, hallucinations, delusions, OCD behaviors (gambling)

2nd generation DA agonist - D3 receptor agonist

Useful prior to starting levodopa as well as with levodopa

Ropinirole metabolized by liver

Fewer side effects - fatigue, nausea, postural hypotension

Ropinirole also used for restless leg syndrome

Biggest problem - sudden sleep attacks in 3% of patients

 Better than dopamine since can penetrate BBB

Converted into dopamine by AAAD in brain

AAAD found everywhere, whereas tyrosine hydroxylase only found in DA neurons, so doesn't help to give tyrosine

Dramatic + immediate improvement in rigidity and akinesia, but no impact on dementia or postural instability

Must be given in large amounts since most of it is processed to dopamine by peripheral AAAD before it gets to the brain

Levodopa + Carbidopa

Carbidopa = peripheral AAAD blocker (AAAD blocker that can't penetrate BBB)

Dose of L-Dopa can be cut in fourths, which greatly reduces the side effects

Levodopa is ALWAYS given in the form of Sinemet

Patients go through peaks + valleys depending on when they took their last pill

Time-release Sinemet available, but not too popular since life never gets too good

After 5 years, will see transient hyperkinsia (chorea, tics) at peak effect since dose needs to keep increasing to compensate for additional neuron loss

Wearing off - doses last shorter and have to be taken more frequently

On-off phenomenon - a dose suddenly and unpredictably wears off

Drug holidays are NOT helpful in preventing the on-off phenomenon

Side effects - anorexia, nausea/vomiting

Autonomic side effects (tachycardia, hypertension, depression, anxiety) from conversion of dopamine into EPI and NE

Should be taken before food (30 minutes) or after (1 hour)

Should be taken with water to aid absorption

 Should not be used with a MAO-inhibitor, since the combined effects will cause greatly elevated peripheral NE levels and a hypertensive crisis

Should not be given to psychotic patients

Anticholinergics can decrease absorption of L-Dopa

COMT inhibitor

COMT in the periphery metabolizes L-Dopa when AAAD is inhibited

Therefore, giving a COMT inhibitor will further improve L-Dopa's effect

Tolcapone - given 2-3/day

Entacapone - can be packaged with Sinemet (Stalevo)

Side effects - dyskinesias, diarrhea, nausea, hallucinations

Tolcapone has significant hepatotoxicity

Entacapone causes orange urine

Antiviral agent that enhances DA release and reduces DA uptake

Can be used alone early or with levodopa later

Side effect - red/purple skin blotches

MAO-B inhibitors - MAO-B is responsible for metabolizing dopamine in the synaptic cleft that is not re-uptaken

Deprenyl - not very effective, but can help a little with the on-off phenomenon

Rasagiline - much more effective, but metabolized in the liver

1) Try amantidine, paramipexole, or ropinirole by themselves

2) When necessary, move to L-dopa, using as low a dose as necessary

3) Once effectiveness begins to drop, decrease dose by combining with a DA agonist (paramipexole/ropinirole), COMT inhibitor (tolcapone/entacapone), or amantidine

Deep brain stimulation - overstimulation of subthalamic nucleus can decrease its output, which can decrease indirect pathway output, causing disinhibition

Used for resting tremors

Mechanism unknown

Switch between/combine options

40-50% of patients show improvement

Other options: primidone, antiseizure medicines, benzodiazepines, glass of wine with dinner, botox

Reserpine/tetrabenazine - inhibits DA uptake into storage vesicles, but causes high rates of depression

Haloperidol, chlorpromazine - blocks DA receptors, but can cause tardive dyskinesia

Fluoxetine - treats the depression associated with HD or caused by HD drugs

Benzodiazepines - treats the spasticity associated with HD

In late stages, Levodopa can help restore some movement

Not really ANY good drugs

Copper chelator that complexes copper and allows it to be excreted in the urine

Can reverse the symptoms of Wilson's Disease, but treatment is lifelong

Trientine used in patients who do not tolerate penicillamine

Copper absorption blockers

Promotes intestinal secretion of a protein with a very high affinity for copper

Cannot use potassium disulfide for maintenance (not effective enough)

However, can start patients on penicillamine for a few weeks to reverse symptoms, then put them on lifelong zinc acetate for maintenance

No really good options

Try DA antagonists like reserpine or tetrabenazine, but be alert for depression

Try DA receptor blockers like haloperidol or chlorpromazine

Try anticholinergics - significant side effects, used more in children, useful for dystonia, NOT useful for chorea

Tourette's syndrome - responds well to haloperidol or clonidine

Female predominance

#1 cause of neurological disability in young adults

Greater risk as you move further from equator

Some genetic component - 1st degree relatives of a MS patient are 20-40x more likely to develop MS

HLA-DR2 allele is associated with an increased risk

Optic neuritis - inflammation of CN II that causes blurry vision, painful eye movements (painful ophthalmoplegia), color desaturation (red), decreased visual acuity, afferent pupillary defect, and papilledema, all unilaterally

Transverse myelitis - inflammation of spinal cord, with parasthesia, weakness, bladder/bowel dysfunction, ataxia, band-like sensation in chest/abdomen, dermatomal sensory loss, and/or UMN signs

Lhermitte's phenomenon - shocklike feeling running down spine when flexing neck

Intranuclear ophthalmoplegia - loss of MLF

Trigeminal neuralgia - typically V2 or V3

Uhthoff's phenomenon - symptoms get worse in hot weather

 Loss of vibratory sense (but not proprioception) in toes - largest fibers get demyelinated first

HTLV-1

Vitamin B12 deficiency

Copper deficiency

Vascular conditions

2 or more episodes separated in time and neurological space

MRI showing periventricular, callosal, brainstem, or spinal cord white matter lesions (Dawson's fingers - lesions perpendicular to the ventricles that radiate outwards)

Relapsing-remitting - most common subtype (80%); 50% of patients progress to secondary progressive

Primary progressive - usually older patients

Secondary progressive - slow progression over 10-15 years, and generally need a walking aid

Progressive-relapsing

Inflammatory immune-mediated disease

Antibodies target myelin and cause demyelin

Primarily T-cell mediated, but B cells are important too

Affects both white and gray matter

Demyelination can cause decreased conduction velocity, scattering of action potentials, and conduction block if severe enough

IV corticosteroids - oral steroids not effective

Plasmapheresis if steroids do not help

Rule out infections/electrolyte imbalances

IV Ig is not effective

Interferon-beta

Glatiramer Acetate - only option with no hepatotoxicity

Natalizumab - only need monthly infusion, but can cause PML (opportunistic JC virus), a fatal disease involving progressive damage/inflammation of white matter at multiple locations

Mitoxantrone - only need infusions every 3 months, but decreases CO and raises risk of leukemia

Fingolimod - can be taken ORALLY once/day, with mild side effects, but still a new drug

Spasticity - initial resistance, but loosens up after (velocity-dependent)

Rigidity - stiff throughout range of motion no matter how fast/slow you move the limb

Spasticity is an UMN sign

Rigidity localizes to the basal ganglia

Skin-covered, very survivable malformation

Occipital encephalocele is the most common form in the US

Female predominance

Survivability depends on how much brain matter is contained in the exposed sac

Most commonly occurs in the thoracolumbar spine

Meningocele - open sac of dura or spinal fluid

Myelomeningocele - sac contains spinal cord or nerve roots

Fixed deficit at level of open spinal cord - anything below won't work

Pregnant women need to take folate supplements to prevent this

Dysplastic skin with spinal cord on outside of body

Opened central canal with exposed nerve roots

Will remain nonfunctional, but should close defect to prevent infection

Can cause extreme hydrocephalus

Diagnosis usually made in utero by looking for alpha fetal protein

Fetal surgery can improve hydrocephalus, but will not prevent neurological deficits

Thickened filum terminale - fat in the filum that pulls on spinal cord and anchors it in place

Lipomyelomeningocele - defect of closure where fat is incorporated in the dura or sometimes in the spinal cord itself

Diastematomyelia - split cord malformation where cord splits around a bony section

Dermal sinus - recurrent meningitis or pimples on back due to a dimple that extends all the way down to the spinal cord

All of these conditions are surgically correctable and have good prognoses

Cerebellar tonsillar herniation down the foramen magnum

Usually asymptomatic and found incidentally on MRI

Can be symptomatic with brainstem compression causing sleeping, swallowing, and/or breathing difficulties

Older children can experience occipital headaches, especially when laughing, sneezing, or coughing (increased ICP)

Can have hydrocephalus, but this is uncommon

No brainstem herniation

Only found in patients with a myelomeningocele

Herniation of cerebellar tonsils and cerebellar vermis

Will see brainstem and cerebral abnormalities

Hydrocephalus is very common

Brainstem (medulla) often gets pulled into the cervical spine along with the cerebellar tonsils

Infants - head enlargement, bulging fontanelle, setting sun sign, scalp vein distension, CN VI paresis

Older children - headaches, nausea/vomiting, diplopia

Chronic - loss of milestones

Transillumination - head lights up due to being full of water

On CT, will see enlarged ventricles

A large cyst in the 4th ventricle causes a large posterior fossa with a small cerebellum

Obstructs the flow of CSF, so also causes hydrocephalus

Total intracranial volume must remain constant

So when one of the three compartments increases, the other two must decrease

The three compartments: brain, CSF, blood

3 Phases

Spatial compensation - ICP remains relatively constant as CSF/blood is shunted out of brain

Decompensation - at some point, run out of CSF/blood, so ICP starts to rise exponentially

Cerebrovascular collapse - when ICP > MAP, brain is no longer being perfused

Decompressive craniectomy - smaller ones = more complications; opening up dura as well can further decrease ICP

Evacuation of mass lesion

Postural changes - elevating the head above the heart to increase venous return and decrease cerebral blood volume

Hyperventilation - decreased PaCO2 leads to cerebral vasoconstriction, lowering ICP, but this can cause ischemic injury, esp. in trauma patients who are frequently already hypoxic

Ventricular/lumbar drainage of CSF - small volumes can reduce CSF drastically, but can also cause herniations

Carbonic anhydrase inhibitors - inhibit CSF production + increase drainage, but only used in pseudotumors

Mannitol - omsmotic diuretic that facilitates cerebral water movement, but leads to dehydration, so need to give IV fluid bolus afterwards

Steroids - decrease vasogenic edema in intra-axial brain tumor patients

Similar to those in hydrocephalus

Headache + projectile vomiting early on -> projectile vomiting is also seen in pyloric stenosis, but that is diagnosed by 6 months of age

Bilateral papilledema after 2-3 days -> no visual blurring or reduction of visual fields unless prolonged

CN VI palsy (due to long intracranial course), lethargy, and cerebral herniation

Initially (diencephalon) - lethargy, contracted pupils, setting sun sign, flexor posturing

Next (midbrain/pons) - coma, Cheyne-Stokes breathing, moderately dilated pupils, extensor posturing

Finally (medulla) - widely dilated pupils, flaccid muscles

Initially (CN III) - unilateral pupillary dilation due to loss of parasympathic input from CN III

Next (midbrain/pons) - extensor posturing

Pupillary changes and posturing

Airway (intubation + oxygenation)

Breathing (ventilation + hyperventilation)

Circulation (IV fluids to maintain blood pressure)

Mannitol to drop ICP

Head CT to find/rule out a surgical lesion

CN I most frequently affected in TBI

Basilar fractures - temporal bone, so CN VII/VIII more likely to be affected

In Calvarial fractures, elevation of depressed fracture over a major sinus is contraindicated if patient is awake

Depressed fractures are associated with brain injury

Wet fractures are those with a CSF leak - worried about infection, but most are self-limited

Middle meningeal artery ruptures from skull fractures lead to epidural hematomas

Eyes - open = 4, response to voice = 3, response to pain = 2

Voice - normal = 5, confused = 4, words = 3, sounds = 2

Movement - normal = 6, local response = 5, withdraw = 4, flexor posturing = 3, extensor posturing = 2

GCS 14-15 = normal if CT negative

GCS 9-13 = moderate brain injury

GCS < 9 = severe brain injury

Avoid hypotension

Avoid hypoxia

Mannitol to control ICP, other measures also if ICP > 20

ICP monitoring if GCS < 9 with abnormal CT scan, age > 40, posturing, or hypotension

Cerebral perfusion pressure should be kept between 50 and 70 - above 70, risk for ARDS

Avoid antiseizure medicine to prevent posttraumatic seizures

Hyperventilation to lower ICP

AVOID steroids

Symptoms occur only with positional changes - transient episodes of vertigo caused by stimulation of vestibular sense organs

Middle-aged + older patients, females > males

Lasts seconds to minutes

Cyst-like lesion filled with keratin debris, involving the middle ear and mastoid

Will see progressive hearing loss in the involved ear

Reactivation of latent Varicella Zoster virus

Will see vesicles on tympanic membrane

Episodes can be caused by immunosuppression

Ear/mastoid pain + unilateral hearing loss (acute to subacute onset)

Hardening/thickening of the tympanic membrane caused by age or repeated ear infections

Progressive hearing loss

Initially severe hearing loss, then gets better

Repeated episodes of vertigo, hearing loss, tinnitus, or aural fullness caused by an increased volume of endolymph in the semicircular canals

In late stages, will last just seconds, but early on episodes can last for hours

Preceded by an upper respiratory infection

Inflammation of the labyrinthine sense organs

Initial symptoms are severe but lessen over next several days

May be preceded by an upper respiratory infection

Horizontal nystamus with or without rotatory nystagmus

Late stages will last just seconds, but early on episodes can last for days

Inflammation of the vestibular nerve

A breach between the middle and inner ear

Can be caused by trauma, diving, loud noises, or excessive stool straining

Sneezing (increase in ICP) can provoke vertigo

Episodes can last seconds to hours

Hennebert's sign - vertigo or nystagmus caused by pushing on the tragus and external auditory meatus

Progressive unilateral hearing loss

Can cause vertigo, but will see other symptoms related to migraines, such as episodic headaches, nausea/vomiting, photophobia, and phonophobia

Can be hereditary

Can last anywhere from hours to days

Can be a vestibular Schwannoma, an infratentorial ependymoma, a brainstem glioma, a medulloblastoma, or a neurofibroma

Focal neurologic findings

Either a transient ischemic attack or a stroke

More likely in elderly, especially those with hypertension, diabetes, or hereditary risk factors

Transient ischemic attacks last minutes to an hour, while vertigo caused by a stroke can last for days

Onset of hearing loss is sudden and unilateral

Can cause vertigo

Will see focal neurologic symptoms

In particular, may see multiple symptoms that cannot be explained by a single lesion

In peripheral vertigo, symptoms wane with repeated testing while they persist in central vertigo

First, get patient upright

Then, turn head 30-45 degrees toward side being tested

Patient should keep eyes open and focused on tester

Support patient's head while patient quickly drops supine

Patient should allow neck to hyperextend 20-30 degrees past horizontal while laying down

Positive test if torsional upbeat or horizontal nystagmus is seen after a 2-20 second latency period

Episode can last up to 40 seconds

Commonly parenchymal lesions, especially at gray/white borders

Typically well-circumscribed mass lesions

Causes vasogenic, extracellular edema that can be suppressed with steroids

Common primary sources - lung, breast, melanoma, renal, lymphoma

Hemorrhagic tumors (thin, dark, hemosiderin ring around white lesion) - melanoma or renal cell carcinoma

Extramedullary + extradural

Usually metastasizes from adjacent vertebral bone

Can cause epidural spinal compression either directly or by fracturing a vertebral body

This causes back pain, so cancer patient + back pain = medical emergency

Infiltration of systemic or CNS tumor into subarachnoid space

Can be spread via blood through Batson's vertebral plexus, which runs along posterior pelvis + spinal column

CSF - high protein with low glucose - known as hypoglycorrhachia, which is found in tumor, atypical bacteria, or fungal meningitis

On MRI, see unusual "clumping" of cauda equina roots

Neural infiltration or compression of multiple proximal nerves

Most common symptom is pain, but can also see neurological deficits that correspond to multiple dermatomes, muscles, and/or reflexes

Pancoast tumor - apical lung tumor that commonly causes brachial plexopathy

Retroperitoneal (colon, uterine, ovarian) tumors commonly cause lumbosacral plexopathy

If not a tumor, then other option is radiation fibrosis - radiation damage in the plexus can cause fibrosis or necrosis of nerves

Myochymia - repetitive nerve discharge picked up on EMG that is indicative of radiation injury

Can be caused by an electrolyte imbalance (severe hypo/hypercalcemia

Can be caused by organ dysfunction (hepatotoxicity)

Can be caused by an ectopic hormone-secreting tumor (small cell lung cancer secreting ACTH, for example)

Myopathy

Tremor

Visual blurring

Psychosis

Pseudotumor (headache + visual disturbances)

Cisplatin - peripheral neuropathy of large fibers only, ototoxicity, vestibulopathy

Ifosfamide - encephalopathy

Vincristine - peripheral, cranial, or autonomic neuropathy, often involving the small fibers

Methotrexate - aseptic meningitis, transverse myelitis, encephalopathy, and leukoencephalopathy

Used in acute leukemia treatment

Causes coagulation (triangle sign), but patients do well once they are on anticoagulation therapy

Triangle sign - clot in back of head at the confluence of the transverse and saggital sinuses where they drain into the jugular veins

Signs of triangle sign - headache in back of head with no sensorimotor symptoms

Encephalopathy

Disorders of organ systems that occur due to cancer, but not directly due to the tumor mass or metastasis

An autoimmune reaction in which an antibody in the serum reacts with target nervous system tissue as well as the underlying tumor

A disease of exclusion -> if no other reason can be found for the organ system dysfunction, then look at this one

Some type (anti-Ri) respond to steroids/IV Ig, but for the ones that do not, there is no treatment

Work better on smaller fibers because:

1) Larger SA:volume ratio allows more drug to penetrate

2) Larger myelinated nerves have larger distances between Nodes of Ranvier

Therefore, local anesthetics will hit nerves in this order: sympathetics, temperature, pain, proprioception, sensation, motor function, sacral parasympathetic function

Since some pain fibers go through vagal parasympathetics, patient may still experience some residual discomfort

Because temperature is knocked out easily, a cold alcohol swab can be used to test whether blockage has occurred

Blockage of sympathetics causes vasodilation, which can be useful in patients with ischemic pain

Need to be hydrophobic to get through connective tissue and fat to get to axon

Then, need to be hydrophilic in order to get into ion channel and block it

Therefore, all local anesthetics are weak bases that can be ionized by addition of H+

3 parts - hydrophobic hydrocarbon chain, hydrophilic amine group, and a linking group that is either an ester or an amide

Esters can be metabolized in the blood by cholinesterases, whereas amides have to get to the liver before they can be metabolized

Henderson-Hasselbach: pH = pKa + log ([base]/[conjugate acid])

Therefore, as pKa increases, the ratio of base to conjugate acid must decrease, so there is more ionized drug

Since ionized drug has a harder time getting to the nerve axon, this means drugs with a higher pKa have a slower onset of action

The more lipophilic a molecule is (i.e. the longer its hydrocarbon chain), the longer it will remain in the lipid region surround the nerve axon, and therefore the longer its duration of effect

Therefore, drugs that are more lipophilic are more potent, but since the mechanism of action of its toxicity is the same as the mechanism for its activity, more potent drugs do not have fewer side effects

1) Vascularity of injection site -> this is most important

2) Lipid solubility

3) Presence of sympathomimetic drugs - they cause vasoconstriction, allowing the local anesthetic to remain local for longer

Therefore, giving EPI with the drug allows you to give a lower dose of the drug

However, vasoconstriction of an end-artery (i.e. a finger) can lead to ischemia and necrosis

Also, if too much EPI is given, it can also get into the vasculature and cause tachycardia/arrhythmia

However, because of its systemic effects, it is useful to give a small dose of EPI before injecting the anesthetic to make sure you are not in a vein

A local anesthetic (ester) AND a sympathomimetic

Therefore, cocaine is not used for anesthesia except in nose jobs, where the vasoconstriction is helpful to limit bleeding

Important early side effects - ringing in the ears, patient just "feels funny"

If you continue, patients will have seizures and/or fall into a coma

Chloroprocaine is relatively safe due to a very high rate of metabolism

Cardiac toxicity - can cause bradyarrhythmias and a negative inotropic effect due to conduction block

Lidocaine is actually used therapeutically for ventricular tachyarrhythmias because of this side effect

Allergic reactions are only found to ester drugs (procaine, chloroprocaine, cocaine, and tetracaine)

Procaine is the most commonly allergic drug

Patients can also be allergic to the preservative used with amide drugs rather than the drug itself

Many times when patients claim to be allergic to a local anesthetic, it is actually because they were overdosed or were allergic to the vasoconstrictor used

Spinal reflex - patient jerks away from stimulus

Autonomic response - at level of brainstem, results in sympathetic response

Neuroendocrine response - release of catabolic/stimulant agents like steroids, glucagon, growth hormone, and catecholamines

Inflammatory response at site of trauma

Perception of pain

Facilitated pain transmission - transmission of noxious stimuli up spinal cord -> although signal is blocked before reaching cortex, pain will percolate in spinal cord and can aggravate postoperatively

Local anesthesia/nerve blocks work well since they block the initial stimulus

General anesthesia works less well since it mostly only affects perception of pain, autonomic response, and (somewhat) the spinal reflex

Preferentially distributed to vessel-rich groups (brain, liver, heart, kidney)

Since children have proportionally more VRG than adults, they need relatively higher doses of drugs since the same dose would be spread over more area

Since fat is NOT highly vascular, obese patients do not need higher doses of drugs unless they are taking a drug for a long time where the drug has time to build up in the fat

No structure/function relationship - all that is necessary is that the drug be lipid soluble

General anesthetics work just by taking up space in a nerve cell's lipid bilayer, temporarily displacing or disrupting ion channels

An INSOLUBLE agent builds up partial pressure fastest, so a LOW blood-gas solubility means a faster speed of onset

Speed of onset is the ONLY thing blood-gas solubility determines

Minimum alveolar concentration (MAC) - the amount of drug needed to render 50% of patients paralyzed

A measure of the potency of the drug

Inversely proportional to the oil/gas solubility of the drug

Therefore, drugs with a high oil-gas solubility will have a low MAC and be more potent

Very rapid acting but very weak -> does not produce skeletal muscle relaxation

Therefore, cannot be used by itself

Very few side effects

Significant respiratory depression

Halothane - smells good, but is a negative inotrope that can cause arrhythmias and, more importantly, produces a toxic metabolite that causes severe hepatitis

Isoflurane - negative inotrope, but maintains CO through increased HR and vasodilation, and has no hepatic toxicity, but smells bad

Desflurane - very rapid onset of action (and very rapid recovery)

Sevoflurane - same as desflurane, but smells good, so induction agent of choice when IV is unavailable

Barbiturate with very fast onset of action

Bad respiratory profile, good cardiovascular profile in healthy patients but poor in the sick

Gets metabolized very slowly, so removal from body is very slow -> cannot be continuously infused

Does not produce skeletal muscle relaxation

Mechanism of action probably involves enhancement of GABA

Grade II

More common in middle-aged adults

May have had several years of neurological complaints, often seizures

Lesions unusual to be found anywhere other than the cerebral hemispheres, especially in the white matter

Well-circumscribed masses, often with central calcification

Micro: fried-egg appearance (clear blob of cytoplasm around a nucleus with finely granular chromatin), small caliber "chicken-wire" capillaries, and a very homogenous appearance

Low mitotic activity and slow growth

1p19q gene codeletion - important because tumors with this deletion respond well to chemotherapy/radiation, while those without do not

Most commonly used induction agent

Removed by redistribution/metabolism in liver, but metabolized fast, so can be infused continuously

Same respiratory/cardiovascular profile as thiopental

Painful on injection since it is not water soluble (therefore not ionizable) and must be injected with an organic solvent that is painful

Major advantage is that it can be injected intramuscularly

Main disadvantage is that it produces hallucinations, so cannot be given in large doses

Useful in emergency situations where there is no time to find a vein, or when a patient does not want to be injected

Potent central respiratory depression

No cardiovascular effects

Only drugs that can prevent the pain facilitation pathways

Also have a good effect on the neuroendocrine response

Addiction is generally not a problem in the hospital setting

Sedative/Amnesic

If injected first, can prevent patients from remembering the painful injection of propofol

Abolishes spinal reflex - good because patient no longer moves, but bad because it is difficult to judge whether patient remains aware or not

In either case, patient does NOT experience pain, but may be able to remember conversations

1) Preganglionic sympathetics (type B)

2) Pain + temperature (type A-delta)

3) Dull pain + temperature (type C - only unmyelinated nerves in this list)

4) Proprioception (type A-gamma)

5) Touch + pressure (type A-beta)

6) Motor (type A-alpha)

Most common glioma (which is most common primary CNS tumor)

Mostly found in the cerebrum, but can also be found in the brainstem and cerebellum

Can be found in any age group

Non-infiltrating, grade I

Typically found in children or young adults (JPA = < 10 years)

Usually located in the cerebellum, and often midline, or just behind the eyeball

Cystic tumor

Micro: bipolar cells w/ long, hair-like processes that are GFAP+ and form dense fibrillary networks

Rosenthal fibers and eosinophilic granules often present

No necrosis/mitotic figures

Tumor grows very slowly and can be resected

Found in temporal lobe of children + young adults

History of seizures

Well circumscribed with highly atypical nuclei

Low-grade tumor with 5-year survival of 80%

Grade II - poorly defined tumor that expands and distorts the brain, although it can look fairly well-circumscribed on imaging

Mild-moderate increase in glial cellularity, variable nuclear pleomorphism, background of GFAP+ astrocytic processes

Gemistocytic - a subtype featuring pink cytoplasm and off-center nuclei

Microcysts - version that is hypocellular with a myxoid background

Grade III

More densely cellular and more highly pleomorphic

Key is that you start to see mitotic figures

Grade IV - similar to anaplastic, except you also see necrosis and vascular proliferation (glomerular-looking or multi-layered vessel wall structure)

Tumor cells collect along edges of necrotic regions - pseudo-palisading tumor

Bilateral bufferly lesion on gross

Ki-67 and Mib-1 are markers for cells not in G0

High-grade astrocytomas are leaky, so will see ring enhancement

Arise in ependymal-lined ventricular system, including the central canal of the spinal cord (most common location in adults)

Can be grade II or III

Frequently seen in setting of neurofibromatosis type 2

Well-demarcated, but proximity to brainstem means tough to completely resect -> spinal tumors are easier

Rosettes + pseudorosettes form (analogs of embryonic central canal)

Grade I

Found in filum terminale of spinal cord

Contains papillary elements on a myxoid background

Can be completely resected

Mostly supratentorial, especially in the temporal lobe

Present with seizures

Gangliocytoma - dysplastic ganglion cells in irregular groups

Gangliglioma - tumor also includes mixed glial cells (usually astrocytoma)

Mostly slow-growing, and surgical resection is generally effective at controlling seizures

Grade IV - Poorly-differentiated, well-circumscribed, rapid-growing, small, blue, round cell tumor

Mostly found in children, found exclusively in cerebellum and grows to fill the 4th ventricle -> causes hydrocephalus

Individual cells are small with little cytoplasm and hyperchromatic nuclei that may be elongated

Abundant mitotic figures

Homer-Wright rosetes - rosettes that don't surround anything

Only brain tumor that can metastasize - can seed the CSF with tumor cells and metastasize into the cauda equina -> this is called a drop metastasis

Tumor is highly malignant but extremely responsive to radiation, so 5-year survival is a robust 75%

Most common CNS neoplasm in immunosuppressed

Mostly midline, especially basal ganglia

Often multifocal within the brain, but does not metastasize

Associated with latent EBV infections

Aggressive + respond poorly to therapy compared with systemic lymphomas

Better circumscribed than glial tumors but less so than metastatic tumors

Often have significant areas of central necrosis

Diffuse large B cell lymphomas most common

Grade I

Female predominance, dural attachment (dural tail)

Radiation therapy increases risk

Encapsulated with a thin layer of fibrous tissue

May contain calcified psammoma bodies

Spinal - 10:1 female predominance

When multiple meningiomas are present, consider NF2

Often express progesterone receptors and grow faster during pregnancy

Grade II

Presence of mitotic figures OR:

3 of the following:

Hypercellularity

Small cells with a high nucleus:cytoplasm ratio

Prominent nucleoli

Patternless growth

Necrosis

Grade III

Highly aggressive tumor that looks like a sarcoma

Papillary meningioma and rhabdoid meningioma have very high recurrence rates and therefore are also considered grade III

S-100+

A component of NF2 - even sporadic Schwannomas typically have an inactivating mutation on the NF2 gene (merlin, the gene product, restricts expression of EGFR)

Antoni A - elongated cells, hypercellular, presence of Verokay bodies (cell-free areas between regions of nuclear palisading)

Antoni B - hypocellular with microcysts and a myxoid stroma

Often occur at cerebellopontine angle, where they are attached to the vestibular branch of CN VIII and called acoustic neuromas

Nodules on skin with overlying hyperpigmentation

If multiple are present, think neurofibromatosis type 1

Well-delineated masses composed of spindle cells

Stroma is highly collagenized with little myxoid material

Associated with neurofibromatosis type 1

Infiltrative lesion growing within a peripheral nerve

Can result in significant neurologic deficits if a major nerve trunk is involved

Have a significant potential for malignant transformation

Not possible to separate lesion from involved nerves

Loose, myxoid background with low cellularity

Autosomal dominant

Characterized by neurofibromas, optic nerve gliomas, Lisch nodules (pigmented nodules of the iris), and cafe-au-lait spots (cutaneous hyperpigmented macules)

Increased tendency for neurofibromas in people with NF1 to become malignant

NF1 gene is located on chromosome 17

Course of disease is highly variable

Autosomal dominant

Commonly results in bilateral acoustic Schwannomas or multiple meningiomas

Ependymomas of the spinal cord also occur

NF2 gene is located on chromosome 22

Autosomal dominant

Tend to develop hemangioblastomas (in cerebellum + retina), and cysts involving the pancreas, liver, and kidneys

Predisposed for renal cell carcinoma and pheochromocytoma

Gene is located on chromosome 3

Hemangioblastoma - highly vascularized neoplasms that occur as a mural nodule associated with a large fluid-filled cyst

Cells are vacuolated, PAS+, and contain a lipid-rich cytoplasm

Very inflamed with multiple areas of necrosis that probably result in herniation

Equivalent to simultaneous microstrokes in multiple areas

Fever

Neck stiffness

Mental status changes

Focal neurologic findings

Rash - seen in meningococcal meningitis

Headache/coma/Cheyne-Stokes breathing

Photophobia

Nausea/vomiting

Coma/respiratory abnormalities - Cushing's triad (increased ICP means decreased cerebral perfusion, so to keep it up there is hypertension, which leads to irregular breathing and bradycardia)

Kernig's sign - hamstring spasms so leg can't be straightened

Brudzinski sign - knee bends on neck flexion

Opisthotonus - head is stuck hyperextended due to severe inflammation in spinal cord

Very young + very old

Can be acquired through sinusitis, otitis media, pneumonia, endocarditis, blunt head trauma, or a CFS leak

Most common cause in the US

Vaccine available but not fully protective

20% mortality with therapy

Gram positive diplococci

Older children to young adults

Acquired through epidemics

10% mortality with therapy

Meningococcemia - petechiae that cause skin necrosis

Vaccination causes 87% reduction in infection in children, but only lasts 2-4 years

Antibiotic prophylaxis (ciprofloxacin) for anyone exposed to oral secretions

Intracellular gram-negative cocci

1 month to 4 years

Acquired through sinusitis, otitis media, or CSF leak

Neonates, pregnant mothers, alcoholics, diabetics, or the immunosuppressed

Gram positive, motile, survives at low temperatures

High opening pressure

Very high, neutrophilic WBC count

High protein

Low CSF:serum glucose ratio

Positive gram stain + positive culture, unless patient has been pretreated with antibiotics

PCR is useful in areas where transportation/contamination of samples may be an issue

< 3 months - worried about Listeria, so ampicillin + gentamycin

3 months - 50 years - worried about all but Listeria, so ceftriaxone + vancomycin

> 50 years or immunosuppressed or pregnant - worried about Listeria again, so ampicillin + gentamycin

No role for steroids

Most common cause of aseptic meningitis, especially in young children

Most common in late summer/early fall

Requires vectors + exposure to those vectors

Differential: arbovirus (West Nile), lyme disease, ehrlichia, polio, coxsackie

Mortality < 1% - supportive therapy is sufficient

Presents identical to bacterial meningitis

Associated with primary genital HSV

Self-limited, but acyclovir can help shorten duration of symptoms

Mollaret's meningitis - recurrent episodes of HSV 2 meningitis probably means patient has herpes

Meningitis lasting longer than 4 weeks

Diagnosis: fungal, TB, Lyme, or drugs

Usually a result of reactivation, so get a chest X-ray

Mostly found in HIV+ patients

Tends to cause a basilar meningitis with oculomotor symptoms

Extremely low CSF glucose - only TB and rheumatoid arthritis have this

Typical TB drugs used

Steroids are recommended to drop CNS pressure

Mortality is > 60%

HIV+

Highly sensitive antigen latex agglutination test

Southwest US

Non-Caucasians, pregnant women, HIV+

Diagnosis based on Southwest, aseptic meningitis, AIDS, and no cryptococcus

Ohio + Mississippi river valleys

Subacute presentation with cranial nerve defects

AIDS

Systemic disease with rash, pneumonia, and retinitis

Most common causes worldwide are measles and Japanese B virus

In US, most common cause is HSV-1

Things that can look like encephalitis:

Non-cerebral infection in elderly (sepsis), drugs (intoxication), toxins, and metabolic abnormalities (i.e. severe acute renal failure resulting in severe lactic acidosis + acidemia)

Temporal lobe abnormalities - first inflammation, then destruction

Diagnosis generally by PCR

Acyclovir in high doses can decrease mortality if started early

No vaccine available

CSF will contain old red cells

100% fatal

Worldwide, spread by dogs; in US, spread by bats

Replicates locally for 48 hours, then spreads via PNS to the CNS -> once virus gets there, treatment no longer helps

Furious - wild, foaming at mouth, hydrophobia

Paralytic - necrosis of spinal cord w/ peripheral nerve degeneration

Brain shows Negri bodies

Diagnosis made clinically or by PCR

Treatment - infiltrate wound with rabies Ig, then vaccinate in contralateral deltoid

Can be asymptomatic or cause meningitis or encephalitis

Most prominent in gay male community, but should screen all HIV+, pregnant women, or sexually active teens as well

Secondary syphilis - 40% have symptoms (aseptic meningitis, affecting CN 2-7, and some uveitis)

Tertiary syphilis - 31% asymptomatic, but even their CSF will show aseptic meningitis

33% have meningovascular disease - occurs 5-10 years post-infection, endartery obliterans, causing multiple brain infarcts, stroke, and dementia

66% have parenchymatous disease - paresis over 10-15 years and tabes dorsalis over 25-30 years (ataxic, wide-based gait with footslap)

Also have Argyll-Robertson pupil - "whore's eye" -> accomodates but does not react

Diagnosis - VDRL+

Can treat with just penicillin

Always think of syphilis, then get a RPR (blood test)

Amoeba that likes warm fresh water and pools

Enters CNS directly through cribiform plate

Patient usually child or young adult having trouble in water

Diffuse meningoencephalitis + purulent meningitis

Olfactory lobe involvement results in changes in taste/smell

Coma and death within 1 week

Will see crenated RBCs in CSF

Aka African Sleeping Sickness

Transmitted by the Tsetse fly

Chancre at site of bite within 1-2 weeks

Hemolymphatic stage for a few weeks-months, with fever, malaise, nausea/vomiting, lymphadenopathy, rash, and Winterbottom's sign (occipital lymphadenopathy)

Finally, meningoencephalitic stage after a dormant period - apathy, confusion, somnolence, often starve to death

Same presentation as HIV dementia, so need to check that first (more common)

Usually, this only occurs in those who have been repeatedly exposed

Ubiquitous worldwide infection - 50% of population infected

Transmitted by cat feces, but not immediately infectious

Most animals are susceptible to this disease

Humans ingest spores through undercooked beef or by working in gardens

Congenital infection possible if mother is infected during pregnancy

Effective immune response kills all bugs except those protected in cysts, which reactivate upon immunosuppression

Diagnosis - multiple enhancing lesions in the brain, seropositivity, response to therapy

Can be prevented with once daily trimethoprim sulfa (also protects immunosuppressed against PCP)

Can cause ocular toxoplasmosis - loss of vision (blind spot in middle of eye) + glaucoma

Aka river blindness

Diagnose - cut open a nodule and find worms inside

Blindness develops as a result of immune response to eye being infested with worms

One dose of Ivermectin once/year prevents disease

Once eye is infected, there is nothing that can be done

Stiff face, ataxia, fisting - both hyperkinetic and hypokinetic signs

Due to ritual cannibalism in Papua-New Guinea

Sunburst inclusions made of amyloid protein (it is the amyloid protein that is infectious)

Loss of Purkinje cells

Aka mad cow disease

Cows fed animal protein to stimulate milk production

Vacuolated neurons -> identical to those found in scrapie

Any kind of CNS disease possible -> hypokinetic or hyperkinetic symptoms, but will have UMN findings

Progression is very rapid in most cases, but chronic forms are also known to exist

MRI shows brain atrophy, especially in the cerebellum - cortex shows "worm sign"

Green discoloration of the putamen on gross

Familial in 5% of patients

New variant found in young people (16-20), with a spongy cortex and sunburst amyloid plaques, just like in Kuru

Contiguous spread - from otitis media to temporal lobe, from sinusitis to frontal lobe

Hematogenous distribution - infected thrombi can create multiple abscesses if it breaks apart on way up to brain

Can also be caused by chronic lung disease or endocarditis

Agents - strep - 60-70%, staph aureus 10-15%, bacteroides fragilis 20%, enterobacteriaciae 20%

Abscesses with show up as ring-enhancing lesions

Treated with antibiotics or surgery

Caused by JC virus infection

CT shows non-enhancing white matter lesions with no edema

Often located in periventricular areas and looks like an infiltrating lesion

In an AIDS patient with non-enhancing white matter lesions, only 2 possibilities - either HIV itself (bilateral lesions) or PML (typically unilateral)

In HIV+ patients, aggressive antiretroviral therapy may be useful, but in HIV-, there is no treatment

Prognosis is less than 6 months