Psychiatry Boards Studying

Upper motor neuron injury

Lower motor neuron injury

Ability to identify objects by touch

Thalamus

burning pain on the contralateral side of the body

• Loss of the same half-field in both eyes
• Lesion is on the contralateral side

Temporal lobe

• 1. Aphasia
• 2. Gerstmann Syndrome
• 3. Alexia without agraphia

• 1. Hemi-inattention
• 2. Anosognosia
• 3. Constructional apraxia

• 1. Acalculia
• 2. Agraphia
• 3. Finger agnosia
• 4. Left-right confusion

Contralateral

Contralateral substantia nigra (basal ganglia)

Contralateral Basal Ganglia

Slow, writhing movements

Contralateral Basal Ganglia

Contralateral Basal Ganglia (most often subthalamic nucleus)

Intermittent flailing of the arm and leg on one side of the body

Contralateral Basal Ganglia

Contralateral Basal Ganglia

Brainstem

Brainstem

When looking to one side, ipselateral eye only minimally adducts; contralateral eye abducts with nystagmus

Brainstem

Brainstem (Lower Motor Neurons)

Impaired function of cranial nerves 9, 10, 11, and 12

Ipselateral cerebellum

Ipselateral cerebellum

Cerebellum

Speech in which words are broken into syllables, often with noticeable pauses and spoken with varying force

• Inability to copy simple forms or arrange objects into specific patterns
• Due to inability to integrate visual and motor functions

Bilateral cerebral hemispheres (corticobulbar tract)

Originates in motor cortex, innervates brainstem motor nuclei

• 1. Globus pallidus
• 2. Caudate
• 3. Putamen
• 4. Substantia nigra
• 5. Subthalamic nucleus

• 1. Globus pallidus
• 2. Caudate
• 3. Putamen

Basal Ganglia

• 1. Control muscle tone
• 2. Regulate motor activity
• 3. Generate postural reflexes

Intermittent, randomly-located jerking of the limbs and trunk

Caudate nuclei (atrophy)

• 1. Peresis
• 2. Abnormal deep tendon reflexes
• 3. Babinski

• Stooped posture with shuffling steps
• Stop walking abruptly at times
• Due to loss of executive function; often appear not to remember how to initiate a step

Normal Pressure Hydrocephalus

Parkinson Disease

Small shuffling steps with hypokinesia

Cerebral palsy (occasionally other congenital injuries)

• Narrow-based gait
• Legs are dragged, and toes scrape on the floor
• Hip adductors are tight, causing legs to cross midline while walking

Damage to posterior columns of the spinal cord

Weakness in dorsiflexion causes foot drop

Myopathies, especially Duchenne Muscular Dystrophy

• 1. Midbrain
• 2. Pons
• 3. Medulla

• 1. Basilar
• 2. Vertebral

• 1. Oculomotor nerve (CN3)
• 2. Corticospinal tract

• 1. Contralateral hemiparesis
• 2. Ipsilateral oculomotor nerve (CN3) paralysis

• 1. Contralateral hemiparesis
• 2. Abducens Nerve (CN6) paralysis

• 1. Paralysis of ipsilateral palate (causes dysarthria)
• 2. Ipsilateral facial numbness (pain and temperature)
• 3. Contralateral anesthesia of the body (pain and temperature)
• 4. Ipsilateral ataxia

• 5
• 7
• 9
• 10
• 11

• 1. Spinothalamic
• 2. Sympathetic
• 3. Inferior cerebellar

• 1. Alcohol
• 2. Dilantin (Phenytoin)
• 3. PCP
• 4. Barbituates

Reduced sensitivity to pain and cold

Medial longitudinal fasciculus

Vertebrobasilar Artery System

• 1. Multiple Sclerosis
• 2. Wernicke-Korsakoff Syndrome
• 3. Viral labyrinthitis

• 1. Head
• 2. Neck
• 3. Trunk

Ipsilateral limbs

Other hemisphere is expected to compensate almost entirely (can walk, can't dance)

• 1. Hypotonia
• 2. Pendular reflexes (limb swings several times in each direction)

• 1. Pain
• 2. Temperature

• 1. Positional sense
• 2. Stereognosis

• 1. Phenytoin
• 2. Lithium
• 3. Chemotherapy
• 4. Toluene
• 5. Organic mercury

• 1. Vitamin E
• 2. Thiamine

Antibodies to malignancy cross-react with cerebellar tissue

Friedreich Ataxia

Foot deformity with high arch, elevated dorsum, and retraction of first metatarsal

Friedreich Ataxia

Vertebral Artery

• 1. Ptosis
• 2. Miosis
• 3. Anhydrosis

Damage to sympathetic fibers that innervate one side of the face

Ipsilateral soft palate paresis (uvula deviates toward the contralateral side)

Yes!

Lateral Corticospinal Tract

• 1. Posterior columns
• 2. Lateral Spinothalamic Tract
• 3. Anterior Spinothalamic Tract
• 4. Spinocerebellar Tract

• 1. Fasciculi Cuneatus
• 2. Fasciculi Gracilis

Position and vibrational sensations

Thalamus

Temperature and pain

Thalamus

Light touch

Thalamus

Position and movement sensations

Cerebellum

C4

T4

T10

Hemisection of the spinal cord

• Corticospinal tract:
• 1. Ipsilateral paresis
• 2. Ipsilateral hyperactive deep tendon reflexes
• 3. Ipsilateral Babinski
• Posterior Column:
• 4. Ipsilateral loss of vibration sense
• 5. Ipsilateral loss of position sense
• Spinothalamic Tract:
• 6. Contralateral loss of pain sensation
• 7. Contralateral loss of temperature sensation

Elongated cavity, adjacent to the central canal of the spinal cord, that affects the spinal cord

Cavity within the spine filled with blood; caused by trauma

• 1. Lateral spinothalamic tract fibers are pulled apart where they cross the cord
• 2. Anterior horn cells are compressed

• 1. Neck pain
• 2. Loss of pain sensation in arms and hands
• 3. Loss of temperature sensation in arms and hands
• 4. Loss of muscle bulk in arms and hands
• 5. Loss of deep tendon reflexes in arms and hands

• 1. Syphilis
• 2. B12 deficiency
• 3. Freidrich Ataxia
• 4. Spinocerebellar Ataxias

Loss of position sense due to damage to posterior columns of the spinal cord

• 1. Posterior columns (demyelinated)
• 2. Corticospinal tract (demyelinated)

Multiple Sclerosis

Spastic paresis, with spasticity disproportionately greater than paresis

Inactivates B12, leading to deficiency and damage to posterior columns

Copper deficiency (often due to excess Zinc consumption)

• 1. Tabes dorsalis (syphilis)
• 2. B12 deficiency
• 3. AIDS
• 4. Multiple Sclerosis

Olfactory

Optic

Oculomotor

Trochlear

Trigeminal

Abducens

Facial

Vestibulocochlear (Acoustic)

Glossopharyngeal

Vagus

Accessory (Spinal Accessory)

Hypoglossal

Frontal cortex

Smell

Trigeminal

• Meningioma compresses an olfactory nerve and the nearby optic nerve, causing unilateral blindness and anosmia
• The tumor can affect the frontal lobe, causing personality changes, dementia, or seizures

• 1. Inhaled metals (welders, Zinc in cold remedies)
• 2. Head trauma (shears CN1 at the cribiform plate)

• 1. Parkinson Disease
• 2. Dementia with Lewy Bodies
• 3. Wilson Disease
• 4. Creutzfeldt-Jakob Disease
• 5. Alzheimer Disease

• 1. Cortex (visual information)
• 2. Midbrain (light intensity information)

Oculomotor nerve (CN3)

Parasympathetic fibers that join CN3

Brainstem

Lateral Geniculate Body

Pretectal Area

Both ipselateral and contralateral Edinger-Westphal Nuclei

Ciliary ganglion (which projects to the iris sphincter muscle)

• Dilated; responds slowly to light but accommodates more quickly
• Caused by damage to a ciliary ganglion

Optic nerve

Oculomotor (CN3)

Oculomotor (CN3)

• 1. Dilated pupil
• 2. Ptosis
• 3. Abduction of the eye

Ability to focus on near or distant objects

Dorsal Midbrain

Midbrain

Depression of the eye while turned inward

• 1. Red nucleus
• 2. Cerebral penduncle

Pons

Abduction

Occlusion of a small branch of basilar artery causing small brainstem infarction

Wernicke Encephalopathy

Transtentorial herniation (cerebral mass lesion pushes the anterior tip of the temporal lobe through the tentorial notch)

• 1. Ipsilateral ptosis
• 2. Ipsilateral dilated pupil
• 3. Diplopia
• 4. Contralateral hemiparesis

• 1. Ipsilateral ptosis
• 2. Ipsilateral dilated pupil
• 3. Diplopia
• 4. Ipsilateral ataxia

• Receives outflow from the contralateral cerebellum
• Innervates contralateral arm and leg
• ("Double-cross" so that the cerebellum innervates its ipsilateral arm and leg)

• 1. Ipsilateral abducens nerve paresis (can't abduct one eye)
• 2. Contralateral hemiparesis (affects corticospinal tract)

• Heavily-myelinated tract between the pons and the midbrain
• Connects nuclei of CN3 (oculomotor) and CN6 (abducens) to mediate conjugate gaze

Damage to the Medial Longitudinal Fasciculus

• Abducting eye has nystagmus
• Adducting eye does not cross the midline

Multiple Sclerosis

Diabetic Infarction

• 1. Sharp headache
• 2. Ipsilateral ptosis
• 3. Ipsilateral ocular abduction
• (pupils equal, both reactive to light)

Posterior Communicating Artery

Blindness of the deviated eye in strabismus

Pons

• Originate in midbrain
• Travel through medulla before forming the nerve

• CN5 (trigeminal)
• CN7 (facial)
• CN8 (vestibulocochlear)

• Forehead
• Cornea
• Scalp up to the vertex

Malar area

Lower jaw, except for the angle

• Ipsilateral Trigeminal Nerve (CN5), branch V1, to pons (one cornea is touched)
• Pons to bilateral Facial Nerves (CN7) (both eyes blink)

Trigeminal nerve

Muscles of mastication

Muscles of facial expression

Both!

Contralateral hemisphere

Facial Nerve (CN7)

Glossopharyngeal (CN9)

Olfactory! (not facial or glossopharyngeal)

Ipsilateral facial nerve (CN7)

Contralateral motor cortex

Facial Nerve (CN7)

Impairment of taste sensation

• 1. TCAs
• 2. Acetazolamide
• 3. Levodopa

Hyposalivation

• 1. Cochlear Nerve (carries hearing information)
• 2. Vestibular Nerve (carries balance information)

• Originate at middle and inner ear
• Terminate at bilateral Superior Temporal Gyri of cerebral hemispheres

• Initially high frequencies, difficulty distinguishing between consonants, and impaired speech discrimination
• Later progresses to involve all frequencies

Age-related degradation of the cochlea, not of the CNS or CN8

Pons

• 1. Vertigo
• 2. Nystagmus
• 3. Unilateral tinnitus
• 4. Progressive hearing loss

Medulla

• 1. Dysarthria
• 2. Dysphagia
• 3. Hypoactive jaw reflex
• 4. Hypoactive gag reflex

9th (Glossal), 10th (Vagal), and 11th (Accessory)

• Speech is thick and nasal or absent altogether
• Able to comprehend
• Able to write

• Food can lodge in the trachea or the nasopharyngeal cavity
• Liquids regurgitate through the nose

Can injure the medullary respiratory center, requiring mechanical ventilation

• 1. ALS
• 2. Polio
• 3. Lateral medullary infarct

• 1. Guillain-Barré
• 2. Chronic meningitis
• 3. Tumors along the base of the skull or in the meninges

Damage to the frontal lobe (rather than brianstem in Bulbar Palsy) causes dysarthria and dysphagia

• 1. Jaw jerk and gag reflexes are diminished in Bulbar Palsy, but hyperactive in Pseudobulbar Palsy
• 2. Pseudobulbar Palsy affects the corticobulbar tract (impaired facial expressions)
• 3. Pseudobulbar Palsy affects the corticospinal tract (upper motor neuron signs)

Emotional lability with tearfulness and laughter without underlying mood change

• 1. Amitriptyline
• 2. SSRIs
• 3. Dextromethorphan with quinidine

Temporal lobe

• 1. B12 deficiency
• 2. Tertiary syphilis
• 3. Spinocerebellar ataxias
• 4. Heavy metal intoxication

• Frontal lobe tumor compresses CN1 and CN2 and increased intracranial pressure
• Ipsilateral optic atrophy and anosmia
• Contralateral papilledema

Damage to the sympathetic trunk of the spinal cord, which ascends to the neck and face

Basal Ganglia

• 1. Snout
• 2. Suck
• 3. Rooting
• 4. Jaw Jerk
• 5. Palmomental
• 6. Grasp
• 7. Meyerson sign

• Irregularity in movement or eye trajectory while performing rapid movements
• Causes overshooting or undershooting the target

Midbrain

Medulla

Apraxic

Ataxic

At the level of arms and upper trunk

Lower limbs

Fibular (previously called peroneal)

Left

Parasympathetic

Sympathetic

Anterior Horn

Painful sensations due to neuropathy

Exaggerated painful response to a mildly noxious stimulus

Delayed, then exaggerated and prolonged pain from a noxious stimulus

• Compression of the radial nerve at the spiral groove in the axilla
• Often occurs due to armpit compression when the arm is draped over a chair or when crutches are used

Common Fibular

Median Nerve

Median Nerve

Ulnar Nerve

Ulnar Nerve

Radial Nerve

Radial Nerve

Radial Nerve

Femoral Nerve

Femoral Nerve

Sciatic Nerve

Sciatic Nerve

Sciatic Nerve

Fibular Nerve

Fibular Nerve

• 1. Atrophy of thenar muscles
• 2. Impaired fine movements of the first 3 fingers

• 1. Diabetes
• 2. Vaculitis
• 3. Lead intoxication

• Simultaneous or stepwise development of peripheral nerve injuries, often including cranial nerves
• Usually due to systemic illness

• 1. Acute intermittent variegate porphyria (causes mental status change)
• 2. Diabetes
• 3. Uremia (causes mental status change)

• 1. Celiac Disease
• 2. Combined System Disease (causes mental status change)
• 3. Alcoholism (causes mental status change)
• 4. Malabsorption
• 5. Starvation

Vitamin B6

• 1. Antibiotics
• 2. HAART medications
• 3. Dapsone
• 4. Isoniazid (causes mental status change)
• 5. Nitrofurantoin
• 6. Antineoplastic agents

• 1. Ciguatera fish poisoning (causes mental status change)
• 2. Arsenic
• 3. Lead
• 4. Mercury (causes mental status change)
• 6. Thallium
• 7. Nitrous Oxide (causes mental status change)
• 8. N-hexane
• 9. Toluene (causes mental status change)

• 1. Mononucleosis
• 2. Hepatitis
• 3. Lyme Disease (causes mental status change)
• 4. Leprosy
• 5. Syphilis (causes mental status change)
• 6. AIDS (causes mental status change)

• 1. Lupus
• 2. Polyarteritis (causes mental status change)

• 1. Adrenoleukodystrophy (causes mental status change)
• 2. Metachromatic leukodystrophy (causes mental status change)
• 3. Spinocerebellar ataxias

• 1. C. Jejuni
• 2. HIV
• 3. Lyme
• 4. Mononucleosis
• 5. Hepatitis
• 6. CMV
• 7. West Nile Virus

• Initially, paresthesias/numbness in fingers and toes
• Next, flaccid paresis of lower limbs
• Ascend to affect upper limbs
• May progress to respiratory insufficiency
• Rarely, progress to involve cranial nerves (first bulbar, then facial, eventually ocular paresis)
• Mental status is never affected!

• Elevated proteins
• Few WBCs

Resolves completely in 3 months as PNS myelin is regenerated

• 1. Plasmapheresis
• 2. IVIG
• Not steroids!

• 1. Bladder
• 2. Bowel
• 3. Sexual

Multiple Sclerosis (occurs because oligodendrocytes are inflamed, not killed, during most flares)

• "Stocking-glove" sensory loss
• Loss of ankle jerk and eventually knee jerk reflexes
• Minimal motor loss

Causes damage to vessels, potentially leading to infarcts and multi-infarct dementia

• Mononeuropathy or polyneuropathy (bilateral wrist or foot drop is common)
• GI distress
• Not cerebral effects!

• 1. White bands across fingernails (Mees Lines)
• 2. Hyperpigmentation
• 3. Hyperkeratosis

Arsenic

Mercury

Dark blue or black line along the gums

Thallium

Vitamin A

B1 (Thiamine)

B2 (Riboflavin)

B3 (Niacin)

B6 (Pyroxidine)

B9 (Folic acid)

B12

E

A

B6 (pyroxidine)

Copper

• 1. Absent DTRs
• 2. Loss of position sensation

• 1. Amnesia
• 2. Dementia
• 3. Cerebellar degeneration
• 4. Peripheral neuropathy

• 1. Dementia
• 2. Dermatitis
• 3. Diarrhea

Demyelination of CNS and PNS neurons

• 1. Polyneuropathy
• 2. Cognitive impairment
• 3. Sensory loss

Posteroir columns

B12 deficiency (NO inactivates B12)

• 1. Hypopigmented skin patches are anesthetic
• 2. Anesthesia of fingers and toes
• 3. Palpable nerves
• 4. May affect large nerves, either individually or in groups

• 1. Facial nerve paresis (unilateral or bilateral)
• 2. Paresthesias (ranging from mild to full unilateral paralysis)

• 1. Headache
• 2. Delirium
• 3. Signs of meningitis/encephalitis

• 1. Pleocytosis
• 2. Elevated protein
• 3. Low glucose
• 4. Lyme antibodies

AIDS

• 1. Distal, symmetrical dysesthesias
• 2. Numbness of soles of the feet
• 3. Mild ankle and foot weakness (loss of ankle jerk)

• 1. Quadriparesis
• 2. Abdominal pain
• 3. Psychiatric symptoms in 25-50%

• 1. Urine prophobilinogen
• 2. Urine or serum 5-aminolevulinic acid

Demyelination in both CNS and PNS, worse in CNS

• 1. Colored granules in lysosomes of nervous system, gallbladder, pancreas, and liver
• 2. Demyelination on nerve biopsy

• 1. Personality and behavioral changes (similar to frontal dementia)
• 2. Thought disorders
• 3. Mood disorders
• 4. Cognitive impairment that progresses to dementia

Demyelinated lesions

• 1. Personality changes
• 2. Inattention
• 3. Depression
• 4. Headaches
• 5. Fatigue
• 6. Psychosis
• 7. Cognitive impairment

n-hexane (in glue)

• 1. Toluene (spraypaint, markers) (causes demyelination)
• 2. Nitrous oxide

• 1. Gait is impaired
• 2. Language is perserved

• 1. Caribbean
• 2. Indian Ocean islands

• Initially, nausea/vomiting
• Later, paresthesias, pain, and loss of sensation in all limbs

• Perception of cold objects as hot
• Unique to Ciguatera Toxin ingestion

Loss of anterior horn cells

• Start in one limb, then spread asymmetrically to other limbs
• Eventually, affect face, pharynx, and tongue

• 1. Bladder control
• 2. Bowel control
• 3. Extraocular movements

• In 90%, none!
• In 10%, frontotemporal dementia

Riluzole

• 1. Flaccid quadriparesis
• 2. Muscle atrophy
• 3. Areflexia
• 4. Fasciculations

Type of Spinal Muscular Atrophy that presents in infants

Type of Spinal Muscular Atrophy that presents in children

• Anterior horn cells
• In spinal cord and lower brainstem

• 1. Asymmetric paresis
• 2. Absent DTRs
• 3. Fasciculations
• If bulbar variety:
• 4. Throat muscle paralysis
• 5. Chest muscle paralysis

Fasciculations without weakness, atrophy, or pathologic reflexes. Usually last days to weeks

Bony encroachment causes stenosis of vertebral foramina and, if high enough, of the spinal canal

• 1. Neck pain
• 2. Arm/hand paresis
• 3. Atrophy
• 4. Hypoactive DTRs
• 5. Fasciculations

• 1. Leg weakness
• 2. Spasticity
• 3. Hyperreflexia
• 4. Babinski

• 1. Low back pain
• 2. Sciatica
• 3. Fasciculations of legs and feet
• 4. Paresis of legs/feet
• 5. Atrophy of lower limb muscles
• 6. Knee/ankle areflexia

Pain/weakness of legs only with walking

• ALS affects facial, pharyngeal, and tongue muscles
• Spondylosis causes neck or back pain and sensory loss

• Abrupt onset of pain radiating down a nerve's distribution
• May have sensory loss or weakness, but may not

• L4-5
• L5-S1

• 1. Flaccid paresis of one or both legs
• 2. Perineal pain/anesthesia
• 3. Incontinence
• 4. Sexual dysfunction

Acute Intermittent Porphyria

Phenothiazines

• 1. Barbiturates
• 2. Phenytoin

• 1. Extraocular movements
• 2. Pupil function

L5-S1

Multiple Sclerosis

Acute Intermittent Porphyria

Antibodies attack ACh receptors

• Cholinesterase inhibitor
• Used to treat Myesthenia Gravis

• Cholinesterase inhibitor, given IV or IM
• Used to treat Mysethenia Gravis (when severe)

• 1. Cholinesterase inhibitors (-stigmine)
• 2. Steroids
• 3. Plasmapheresis
• 4. IVIG
• 5. Immunosuppressants

Blocks release of ACh at synapses

Binds ACh receptors, inactivating them

• Cholinesterase inhibitor (the only one that crosses the blood brain barrier)
• Treats Alzheimer Disease or Anticholinergic Syndrome

• 1. Oculomotor muscles
• 2. Facial muscles
• 3. Bulbar muscles

• Young women
• Older men

• Nasal tone to voice
• Grimace instead of smiling
• Difficulty chewing
• Difficulty whistling

• 1. Ptosis
• 2. Neck/facial muscles
• 3. Muscles of the trunk (neck, shoulder, swallowing, and respiratory; bulbar palsy)
• 4. Respiratory distress, quadriplegia, inability to speak (severe cases)
• 5. "Locked in" state (very severe cases)

• Extraocular only!
• Intraocular are not affected!

No!

• 1. Illness, (classically pneumonia)
• 2. Psychologic stress
• 3. Pregnancy

• 40% have an exacerbation
• 30% enjoy remission

Proximal

Normal tone, but muscles are tender

Normal or hypoactive

Neuromuscular Junction

• Used to test for myesthenia gravis
• Give IV cholinesterase inhibitor (edrophonium)
• If symptoms improve, test is positive

Antibodies attack calcium channels, blocking release of ACh from presynaptic neurons

• 1. Small cell carcinoma of the lung (or other cancers)
• 2. Rheumatologic illness

Starts with weakness of limbs, then affects the trunk later

Lambert-Eaton Syndrome (repeatedly attempting to move provokes more ACh release)

Lambert-Eaton Syndrome

• 1. Ocular (including dilated pupils)
• 2. Bulbar
• 3. Respiratory

Nausea, vomiting, diarrhea and fever

18-36 hours later

Blocks presynaptic release of GABA and glycine, reducing inhibition of motor neurons

Antagonizes GABA and glycine receptors, reducing inhibition of motor neurons

Trismus occurs in tetanus, but not in strychnine poisoning

Bind and inactivate Acytylcholinesterase (AChE), causing muscle contractions and fasciculations, and eventual paralysis of the diaphragm

Bind and inactivate Acytylcholinesterase (AChE)

• 1. "Outpouring of fluids" (tearing, pulmonary secretions, diarrhea)
• 2. Miosis
• 3. Convulsions (or seizures)
• 4. Altered mental status (ranging from delirium to unconsciousness)
• 5. Respiratory depression
• 6. Bradycardia
• 7. Hypotension

• 1. Pyridostigmine (reversible AChE inhibitor that competes with the toxin, which is an irreversible inhibitor)
• 2. Atropine
• 3. Oximes (reactivate AChE)
• 4. Benzodiazepine if concern for seizures

Affect large, proximal muscles first, most severely, and often exclusively

• X-linked
• 30% are de novo mutations

• Thighs (difficulty standing)
• Shoulders

Increase in size, as they are infiltrated by fat and connective tissue (pseudohypertrophy)

Steroids (delay progression)

Dystrophin

• Variant of Duchenne Muscular Dystrophy
• Dystrophin retains some function
• Weakness begins in 2nd decade and progresses slowly

Myotonic Dystrophy

• Age 20-25
• No sex preference

• Facial and distal limb muscle weakness/atrophy
• Involuntary prolonged muscle contraction

• Sunken, elongated face (facial and temporal muscle wasting)
• Ptosis
• Prominent forehead
• Frontal balding

• 1. Cataracts
• 2. Heart conduction abnormalities
• 3. Endocrine organ failure (infertility, diabetes)

• 1. Phenytoin
• 2. Quinine

• Nearly always present, and worsens with age
• Lack of initiative
• Progressively bland personality

Fragile X Syndrome

Friedreich Ataxia

• 1. Sponocerebellar atrophy
• 2. Huntington Disease
• 3. Myotonic Dystrophy

Sperm are more likely than eggs to increase the number of trinucleotide repeats that they carry

• Inflammatory myopathy
• Causes weakness, myalgia, and fever

Symptoms of inflammatory myopathy accompanied by a rash

Typically on face and extensor surfaces the elbows and knees

Viral illness

Inflammatory diseases (eg polymyalgia rheumatica)

Ingestion of large amounts of tryptophan

• 1. Several days of myalgia
• 2. Fatigue
• 3. Rash
• 4. Neuropathy
• 5. Cardiopulmonary issues

• 1. Myalgia
• 2. Weakness
• 3. Fatigue
• 4. Weight loss

• Proximal weakness and wasting
• Cushingoid symptoms

Potassium (hypokalemic myopathy)

• 1. Confusion/agitation/stupor
• 2. Seizures

• Areflexic quadriparesis occurring for several hours to 2 days
• Remain alert, cognizant, and able to breathe normally
• Extraocular movements are preserved

• 1. Exercise
• 2. Sleep
• 3. Large carbohydrate meals

Autosomal dominant

Irreversibly inactivates mitochondrial respiratory enzymes

Deficiencies in mitochondrial enzymes in muscle

• 1. Weakness/exercise intolerance
• 2. Short stature
• 3. Seizures
• 4. Deafness
• 5. Episodic lactic acidosis

• 1. Ptosis and extraocular muscle palsises
• 2. Retinitis pigmentosa
• 3. Short stature
• 4. Cardiomyopathy
• 5. Endocrine anomalies

Hereditary optic atrophy in young men

• Intermittent or progressive mental status abnormalities (dementia or delirium)
• First occur between infancy and 12 years of age

• 1. Paresis of extraocular muscles
• 2. Psychomotor retardation
• 3. Migraines
• 4. Optic atrophy

Accumulations of diseased mitochondria

• 1. Coenzyme Q10
• 2. Bone marrow transplant

• 1. Delirium
• 2. Extrapyramidal signs
• 3. Autonomic hyperactivity

• Rigidity
• Tremors
• Dystonic posturing

• High fever
• Tachycardia

Muscles flex so strongly that rhabdomyolysis occurs, leading to kidney failure

Damage to cerebral cortex

• Sudden drop in effects of dopamine
• Either by blocking dopamine receptors, depleting dopamine, or stopping dopamine supplementation abruptly

• 1. Bromocriptine
• 2. Apomorphine
• 3. Amantadine
• 4. L-Dopa

Myoclonus and tremulousness

• 1. Ecstasy
• 2. Amphetamines
• 3. Cocaine

• 1. Deprenyl
• 2. Rasagiline

Triptans

Cyproheptadine

Excessive calcium release

Anesthetics (inhaled, as well as succinylcholine)

Dantrolene

• 1. Phencyclidine
• 2. Anticholinergics

Reduced conduction velocity

Reduced amplitude

Muscles are noted to have deteriorated

• 1. Lactic dehydrogenase
• 2. Aspartate aminotransferase
• 3. Aldolase
• 4. Creatine Kinase

Neuroleptic Malignant Syndrome

• 1. Hyperthyroidism
• 2. Thymoma

• 1. Disulfiram
• 2. Chlorpromazine
• 3. Nitrofurantoin
• 4. Isoniazid
• 5. Vitamin B6

• 1. Chlorpromazine
• 2. Statins
• 3. Nucleoside analogues

Hypokalemia

Pneumonia

Amnesia that is both anterograde and retrograde

• 1. Behavior disturbance
• 2. Depressed mood
• 3. Headache

• 1. Ataxia
• 2. Peripheral neuropathy

• 1. Amnesia
• 2. Personality changes
• 3. Complex partial seizures
• 4. Klüver-Bucy Syndrome

• Enters through nasopharynx
• Attacks frontal and temporal lobes

• 1. GHB
• 2. Scopolamine
• 3. Zolpidem (Ambien)

Cortex

• 1. Recall of newly-learned lists
• 2. Shortened attention span
• 3. Slowed learning
• 4. Decreased ability to perform complex tasks

Slowing of alpha waves

• 1. Decreased frontal/parietal volume
• 2. Cortical atrophy
• 3. Expansion of Sylvian Fissure
• 4. Expanded lateral and 3rd ventricles
• 5. White matter hyperintensities

• 1. Paraneoplastic syndromes
• 2. Vasculitis

• 1. HIV
• 2. Creutzfeldt-Jakob disease (CJD)
• 3. Subacute sclerosing panencephalitis

• 1. Adrenoleukodystrophy
• 2. Wilson Disease

• 1. Huntington Disease
• 2. Metachromatic Leukodystrophy

Autosomal dominant

Autosomal Dominant

Autosomal Dominant

Autosomal Recessive

• 1. HIV-associated dementia
• 2. Frontotemporal dementia
• 3. Lewy Body dementia
• 4. Paraneoplastic encephalitis
• 5. Creutzfeldt-Jakob Disease

• 1. Apathy
• 2. Affective change
• 3. Slowed mental processing
• 4. Gait abnormalities
• 5. Extrapyramidal motor abnormalities

• 1. Parkinson Disease
• 2. NPH
• 3. HIV-associated dementia
• 4. Vascular dementia

• 1. CBC
• 2. CMP
• 3. B12
• 4. HIV test
• 5. RPR
• 6. Lyme titers
• 7. TSH
• 8. Apo-E

• CT is better for screening
• MRI is better for ruling out other causes of symptoms

Generalized slowing; difficult to distinguish from age-related changes most of the time

• Not done routinely
• Can be used to rule out infectious causes or NPH

• 1. PET scan
• 2. Lumbar puncture for amyloid and tau protein

• Impairment of either memory or nonmemory functions
• Can still function independently
• 10% progress to Alzheimer Disease each year
• 30% will never progress to dementia

• Difficulty with word finding
• Use of incorrect words
• Circumvent forgotten words

Inability to find a word

Use of an incorrect word

• 1. Hemi-inattention
• 2. Left homonymous hemianopsia
• 3. Aprosody

• Occurs in 20-40%
• Often paranoid ideations

• Occur in ~10%
• Mostly visual
• Sign of poor prognosis

Anosmia

• 1. Parietal-temporal junction
• 2. Limbic System (especially hippocampus)
• 3. Locus Ceruleus
• 4. Olfactory nerve

Amyloid beta peptide

Tau

• Nucleus Basalis of Meynert
• Depletes ACh

20%

• 1. E3-E4
• 2. E4-E4

• 1
• 14
• 21

• Donepazil
• AChE inhibitor

• 1. Parkinson Disease
• 2. Alzheimer Disease
• 3. Lewy Body Dementia

Cholinesterase inhibitors (that cross the blood-brain barrier)

• Improved memory and learning, less agitation/aggression
• May reverse the process of apoptosis

NMDA receptor antagonists

• AD affects ACh pathways
• Antidepressants that have cholinergic effects can have exaggerated side effects

• 1. Olanzapine
• 2. Risperdal

Alzheimer-like condition occurs around age 50 in nearly all cases

Fivefold increased risk

• Core of α-synuclein and ubiquitin
• Surrounded by loose fibrils

Lewy Body Dementia

Parkinson Disease

Reduced in both; greater reduction in Lewy Body Dementia

5

Temporal lobes

50% have REM Sleep Disorder, in which their limbs are not paralyzed during REM sleep

Even at low doses, cause significant extrapyramidal signs

• 1. Parkinsonism
• 2. Visual hallucinations
• 3. Fluctuating cognition

Frontal lobe

Absence of speaking and expression due to absent voluntary movements

Frontal lobe (these symptoms are due to inhibition!)

Little, if any impairment

• 1. TBI
• 2. Glioblastoma multiforme
• 3. Metastatic tumor
• 4. Metachromatic leukodystrophy
• 5. MS
• 6. Anterior Cerebral artery aneurysm/infarction

• Onset often in mid-50s
• Fatal course lasting less than 4 years

Frontal lobes

Anomia

• 1. Anomia
• 2. Paraphasia
• 3. Decreased fluency

Frontal and temporal lobe atrophy

• Can copy a picture well
• Can not draw a picture from memory

Frontotemporal dementia

Chromosome 17

Progressive Supranuclear Palsy

60-70

Progressive decline over approximately 7 years

• 1. Executive dysfunction
• 2. Reduced verbal output
• 3. Pseudobulbar palsy
• 4. Parkinsonism (without tremor)

Axial rigidity forces entire spine to be upright and unnaturally straight, leading to instability and falls

• First lose ability to voluntarily look upward, then lose ability to voluntarily look laterally
• "Doll's eyes" are preserved

• 1. Basal ganglia
• 2. Frontal cortex
• 3. Upper brainstem

Physical findings

Cholinesterase inhibitors

• 1. Short-term memory
• 2. Abstract reasoning
• 3. Visual dexterity
• 4. Psychomotor dexterity

Mainly anterograde

• 1. Conjugate gaze paresis
• 2. Abducens nerve paresis
• 3. Nystagmus

• 1. Mamillary bodies
• 2. Periaqueductal gray

• 3rd
• 6th

Injection of Thiamine (B1)

• 1. Dementia
• 2. Gait apraxia
• 3. Urinary incontinence

Temporal horns

Gait, but usually not dementia, improves

Internal Capsule

• Fail to alternate leg movements
• Do not shift weight to forward foot
• Foot may tremor and appear "magnetized" to floor when stepping because weight remains on it

• 1. Dementia
• 2. Hallucinations
• 3. Thought disorder

• 1. Dysarthria
• 2. Tremor
• 3. Argyll Robertson pupil
• 4. Hearing loss
• 5. Vision loss

Latent or mutant measles (rubeola) virus infection of neurons

12 years

Behavioral disturbances and personality changes deteriorating into dementia

• 1. Weakness starting in one limb, progressing to full-body paralysis with myoclonus
• 2. Choreoathetoid movements
• 3. Seizures
• 4. Coma and death

• Most live 1-2 years
• Only 5% survive 5 years, usually in a vegetative state

CSF measles antibody titer

Intranuclear eosinophilic inclusions

• Intracytoplasmic
• Eosinophilic

• 1. Dementia
• 2. Myoclonus
• 3. Periodic EEG patterns

50-64

6 months

• 1. Pyramidal signs
• 2. Extrapyramidal signs
• 3. Cerebellar signs

Familial prion disease

Periodic sharp-wave complexes or a burst suppression pattern

• 1. 14-3-3 protein is present
• 2. Tau is elevated

Brain biopsy

Psychiatric disturbances: dysphoria and anxiety progressing to aggression and thought disorder

• Painful paresthesias with myoclonus
• Dementia
• Decorticate posture

14 months

Pharyngeal tonsil

• 1. Headache
• 2. Peripheral neuropathy
• 3. Radiculopathy
• 4. Meningitis
• 5. Encephalitis

• 1. ↑ Lymphocytes
• 2. ↑ Protein
• 3. ↓ Glucose
• 4. Lyme antibodies

• 1. Duration of HIV illness
• 2. Low CD4 count
• 3. Viral load
• 4. Anemia
• 5. Thrombocytopenia
• 6. HepC coinfection

Rapid, over weeks to months

• 1. Memory
• 2. Attention
• 3. Psychomotor speed
• 4. Construction

Psychomotor retardation and clumsiness affect gait and dexterity

Persistent vegetative state

• 1. HAART
• 2. Stimulants
• 3. Antidepressants

• 1. Central atrophy with enlarged ventricles
• 2. Basal ganglia abnormalities
• 3. Nonspecific abnormalities in white matter

Cerebral Toxoplasmosis

Cerebral Toxoplasmosis

Antibiotics

JC Virus infecting oligodendrocytes

Multiple white matter lesions that eventually become confluent

• 1. Cognitive impairment
• 2. Hemiparesis
• 3. Spasticity
• 4. Blindness
• 5. Ataxia

PCR shows JC virus DNA in CSF

• 1. JC virus
• 2. Candida
• 3. Aspergillus
• 4. CMV
• 5. Polyoma virus

Primary cerebral lymphoma

• Usually a single lesion
• Occur in spinal cord as well as brain

Usually poorly responsive to treatment

Myelitis (paraparesis, Romberg sign, etc)

HTLV-1 (Human t-cell lymphotrophic virus type 1)

Hepatic or uremic

Too-rapid repletion of sodium

• 1. Nystagmus
• 2. Quadriparesis
• 3. Ataxia

• 1. Benzodiazapines
• 2. Opioids
• 3. Nicotine

Mammilary Bodies

Synapse loss

Cervical spondylosis

Autosomal recessive

Autosomal dominant

Autosomal dominant

• 1. Alzheimer Disease
• 2. Progressive Supranuclear Palsy
• 3. Frontotemporal Dementia

• 1. Nucleus Basalis of Maynert (main site)
• 2. Basal forebrain (in the brainstem)

• Anticholinergic
• Crosses blood brain barrier only at high dose

Pre-existing dementia

Bilateral occipital lobes

Pick Disease

Subacute Sclerosing Panencephalitis (SSPE)

• 1. Alzheimer Disease
• 2. Subacute Sclerosing Panencephalitis (SSPE)

• 1. Dementia with Lewy Bodies
• 2. Parkinson Disease

Profound cholinesterase deficiency throughout the cortex

• 1. Profound cholinesterase deficiency throughout the cortex
• 2. Low uptake in basal ganglia

• 1. ↓ Amyloid β
• 2. ↑ Tau

Reticular activating system

• NMDA antagonist
• Used in Alzheimer Disease

Contralateral parietal lobe

Left frontal or parietal lobe

Inability to convert an idea to action

Inability to perform a sequence of steps

Complete or nearly complete loss of speech and other forms of expression

Frontal lobe

Arachnoid villi/granulations

Huntington Disease

Hippocampus

• 1. Parkinsonism
• 2. REM sleep behavior disorder

Nondominant hemisphere

Inject amobarbital directly into a carotid artery; if this carotid is the dominant side, the patient will be temporarily aphasic (Wada Test)

• In musically gifted people, dominant
• In most people, nondominant

Medial Geniculate Body

• Primary auditory cortex
• Located in temporal lobe

Starts at Wernicke's Area, connects to Broca's Area

Temporal

Frontal

Transmits visual information from the Lateral Geniculate Bodies (thalamus) to the Visual Cortex (occipital lobes)

Lateral Geniculate Body

• 1. Sylvian fissure
• 2. Motor cortex's representation of face, throat, and upper extremity

• 1. Wernicke's Area
• 2. Arcuate Fasciculus
• 3. Broca's Area

Telegraphic speech ("jerky" tempo)

• 1. Paraphasic errors
• 2. Circumlocution
• 3. Tangentiality
• 4. Clang associations

• 1. Right hemiparesis (more common in arm/face than leg)
• 2. Visual field cuts
• 3. Oral Apraxia

• 1. Hemisensory loss
• 2. Hemianopsia

Left parietal association region

• 1. Repetition
• 2. Naming
• 3. Comprehension

• Repetition is intact (often involuntarily and sometimes compulsively)
• Comprehension is lost

Similar to Broca's, except repetition is intact

Both comprehension and repetition are lost

Middle Cerebral Artery

Inability to execute normal voluntary movements of the face, lips, and tongue

Watershed region

Hypoperfusion to the brain causes ischemia at regions perfused by distal branches of ACA, MCA, and PCA, causing cortical damage at the intersections between their distributions

Extensive damage to the dominant hemisphere

• Some gestured requests (bypass the language arc)
• No verbal requests

• Gestures (with nondominant hand)
• Shoulder shrugs

• Fluent aphasia
• Comprehension impaired
• Repetition impaired

Similar to Wernicke's Aphasia, but repetition is intact

• Usually, the only deficit is loss of repetition!
• Can sometimes have paraphasic errors or hesitancy

Incorrect or meaningless (possibly nonsensical) words used in speech (ie in fluent aphasia)

Word substitution in fluent aphasia in which a word with a similar meaning is used (ie "spoon" for "fork)

Word substitution in fluent aphasia in which an entirely unrelated word is used

Connection of words based on them sounding similar, rather than by meaning

• 1. Hyperactive reflexes
• 2. Babinski
• 3. Field cut

Fluent Aphasia

Small stroke in the angular gyrus

• Embolic stroke in left parietal or temporal lobe
• Usually so small as to cause no other deficits

Schizophrenic patients can repeat polysyllabic words and complex phrases; patients with fluent aphasia can not!

• 1. Dominant occipital lobe
• 2. Posterior corpus callosum (splenium)

Angular Gyrus of dominant parietal lobe

Inability to carry out a learned action despite normal strength, sensation, and coordination

Nonfluent aphasia

Dementia, especially Frontotemporal Dementia

Nondominant

Nondominant

Normal pressure hydrocephalus

Nondominant

Form of hemi-inattention in which the nondominant hand retains semi-purposeful actions outside of the patient's control

Nondominant parietal lobe

Inability to recognize or impart emotions in speech or expressions

Thick myelin-coated axonal bundle connecting two brain regions

Occlusion of bilateral ACA causes bilateral frontal infarct as well as infarct of the anterior corpus callosum

• Nondominant limbs have normal spontaneous movement, but can not be moved if asked to do so
• (language cortex from dominant hemisphere can't transmit to nondominant motor cortex)

• 1. Deafness
• 2. Ataxia

• 1. Delirium
• 2. Ataxia/loss of DTRs
• 3. Palsy of CN6
• 4. Bilateral nystagmus

• 1. Delirium
• 2. Ataxia

• Denial of blindness
• Patient confabulates about objects presented to them

Denial and confabulation

Nasal speech

Hypophonia

Strained/stangled speech

• 1. Aphasia
• 2. Right Homonymous Hemianopsia

• 1. Aphasia
• 2. Right Homonymous Hemianopsia

Relays information about light intensity to adjust pupil size

Loss of proprioception

Tension Type Headache

• Women > men
• Tends to run in families

OTC medications (NSAIDs, acetaminophen, caffeine, etc)

Migraine

• Women > men (3x more often)
• Increasing prevalence until age 40, but can start in childhood

• Evolve over 5-20 minutes
• Last less than an hour

• Temporal, periorbital, or retroorbital
• Usually unilateral, but rarely always on the same side

4-72 hours

Often evolve into chronic dull, symmetric pain that mimics Tension Type Headache but has nonheadache symptoms of migraines

Early morning, often beginning during sleep

Afternoon

• Often first develop at menarche
• Attacks are often most likely to occur before or at the beginning of menses
• Most women's migraines improve during pregnancy, but some worsen

Migraine

• 1. More severe
• 2. Briefer (often less than 2hrs)
• 3. Less often unilateral

• (cerebellar/posterior cerebral/brainstem distribution)
• 1. Ataxia
• 2. Vertigo
• 3. Dysarthria
• 4. Diplopia
• 5. Transient memory impairment (rare, if temporal lobes are affected)

• 1. Hemiparesis and anesthesia
• 2. Aphasia
• 3. Cortical symptoms

Paralysis/paresis while postictal

Chromosome 19

Migraine with Aura

• 1. Triptans
• 2. Ergot derivitives (ergotamine, DHE)

Vasoconstriction cause fetal malformations or miscarriage

Precipitate serotonin syndrome

Dystonic reactions (similar to antipsychotics)

Migraine attack lasting greater than 3 days

• 1. 4+ headaches per month
• 2. 3-4 disabled days per month
• 3. Acute medications losing efficacy
• 4. Taking excessive medicine

• 1. TCAs
• 2. β-blockers
• 3. Anti-epilleptics

• 1. Topamax
• 2. Valproate

No!

Yes!

• Headaches lasting 4+ hours
• 15 days per month
• 3+ months

Dull, pressing, waxing and waning (but not pulsatile)

Medication overuse

Cluster Headache

45-90 minutes

Men aged 20-40

• Between 9PM and 9AM
• 1/2 develop during REM sleep

• 1. Oxygen
• 2. Triptans
• 3. Calcium channel blockers
• 4. Ergot derivatives
• (must be given IV or IM - PO are absorbed too slowly)

• 1. Lithium
• 2. Steroids
• 3. Verapamil
• 4. Depakote

Patients older than age 55

Temporal Arteritis

• 1. Malaise/low grade fever
• 2. Weight loss
• 3. Myalgia/arthralgia

Arterial inflammation causes arterial occlusion, leading to blindness or stroke

• 1. ESR
• 2. CRP

High-dose steroids (if suspected, give before labs are back!)

• Cognitive and personality changes are often subtle, but nearly always present
• Lateralized signs within 8 weeks

Facial palsy, extraocular muscle palsy, and hearing impariment due to strangulation of CN3-8

Young, obese women with irregular menses

Idiopathic Intracranial Hypertension

• 1. Enlarged scotoma, eventually causing blindness
• 2. Abducens palsy

Cerebral swelling with compressed, "slit-like" ventricles

• 1. Very high CSF pressure (over 20cm H₂O)
• 2. Low protein (diluted by edema)
• 3. Normal glucose
• 4. No cells

• Repeated LPs
• If LPs are not effective, shunt placement

• 1. Meningococus (in children)
• 2. Pneumococcus (in adults)

• Occurs in older patients
• Insidious onset
• Subtle signs

HSV

Underside of temporal and frontal lobes

• 1. Complex partial seizures
• 2. Memory impairment
• 3. Aphasia
• 4. Frontal lobe behavior disorders

Arteries comprising the Circle of Willis

Hypertensive crisis that can cause aneurysms to rupture

• 1. Triptans
• 2. Demerol (meperidine)
• 3. L-Dopa
• 4. Carbamazapine
• 5. TCAs

• 1. Phentolamine
• 2. Chlorpromazine
• 3. Propranolol

Trigeminal neuralgia

V2

Women over age 60

Daytime; often abates at night, allowing full nights of sleep

• 1. Initially, Gabapentin or Pregabalin
• 2. Antiepilleptics (especially carbamazepine and oxcarbazepine)
• 3. Pain medications (NSAIDs, TCAs, opiates, lidocaine patches, benzodiazepines)

Mitochondrial encephalopathy

• 1. Depressed sensorium/inattention
• 2. Daily dull headaches
• 3. Anxiety/depression
• 4. Nausea/vomiting
• 5. Diplopia
• 6. Ataxia

Dorsal Raphe nucleus

CN5 (trigeminal nerve)

• 1. Vascular spasm
• 2. Claudication
• 3. Muscle cramps

CNS infection causing meningitis or brain abscess

Carbonic anhydrase inhibitors (eg acetazolamide)

Fluoxetine

Alpha waves over the occipital region (Posterior Dominant Rhythm)

Beta activity over the frontal lobes

8-13Hz

>13Hz

Beta Waves

4-7Hz

<4Hz

• Children
• Sleeping adults

• Children
• Sleeping adults

Neurodegenerative illness

Irritative cerebral focus

Bursts of spikes, slow waves, or combinations of the two

• Theta and delta activity replaces alpha activity (background slowing)
• Focal areas of hyperactivity

Triphasic waves

Spikes and lateralizing epileptiform discharges in temporal lobes

Very well! Nearly always present, so if not present metabolic encephalopathy can be ruled out!

Delirium

Background activity slows below 8Hz

Periodic sharp-wave complexes

• Periodic sharp-wave complexes (1-2 per second)
• Background slowing

None!

None!

Normal

Slow, disorganized activity

• 1. Brain Death
• 2. Hypothermia (can recover)
• 3. Drug overdose (can recover)

Beta waves

Triphasic waves

If complex, consciousness is altered

Temporal lobe is most common, then frontal lobe

Spread of discharges such that they engulf the entire cerebral cortex

Subcortical structures, such as the thalamus

• 1. Uncus (most common)
• 2. Amygdala

Cerebral cystericosis

Tuberculomas

Late childhood to early adulthood

Complex Partial

• 1. Temporal (vast majority)
• 2. Frontal

Mesial temporal sclerosis

• 1. Sclerosis of hippocampus
• 2. Temporal lobe atrophy

2-3 minutes

Elevated prolactin (occurs in 40% of cases)

Frontal lobe seizures

• Tends to develop in adulthood
• Several seizures per month, mostly during sleep

Frontal Lobe Seizures

Epilepsy

• Occurs several hours after seizures (after a "lucid interval")
• Lasts hours to weeks

Benzodiazepines or antipsychotics

• Arises at age 30-40 in patients with epilepsy since childhood
• Do not deteriorate

• Hallucinations
• Paranoia
• Affect is normal!

• Antiepileptics are the mainstay
• Antipsychotic if antiepileptic is not effective

Chlorpromazine (Thorazine)

Depakote increases Lamictal levels

Side effects can include hyponatremia; if very severe, this can lead to increased seizures

• 1. Benzodiazepines
• 2. Neuroleptics (typical and atypical)
• 3. Tricyclic antidepressants
• 4. SSRIs
• 5. Oral contraceptive
• 6. Methadone

• 1. Benzodiazepines
• 2. Neuroleptics (typical and atypical)
• 3. Tricyclic antidepressants
• 4. SSRIs
• 5. Oral contraceptive

• 1. Alcohol
• 2. Erythromycin
• 3. Various psychotropics

Valproic Acid

• 1. Benzodiazepines
• 2. Tricyclic antidepressants
• 3. SSRIs
• 4. Antiepileptics (especially Lamictal)

• 1. Lamotrigine
• 2. Topiramate
• 3. Levetiracetam

• 1. Phenytoin
• 2. Carbamazepine
• 3. Phenobarbital

Reduce bone density, increasing risk of osteopenia

Acts on osteoblasts, causing bone loss

Stevens-Johnson Syndrome

Carbamazepine in people of Asian ancestry

• 1. Stevens-Johnson Syndrome
• 2. Hepatic abnormalities
• 3. Bone marrow suppression

Valproate

• 1. Topiramate
• 2. Zonisamide

• 1. Nystagmus
• 2. Ataxia
• 3. Dysarthria

• 1. Acute glaucoma
• 2. Calcium phosphate renal stones

• 1. Phenytoin
• 2. Carbamazapine
• 3. Phenobarbital
• 4. Topiramate

Valproate

• 1. Valproate
• 2. Carbamazapine

• 1. Lamotrigine
• 2. Levetiracetam
• 3. Oxcarbazapine
• 4. Topiramate

Neural tube defects

Ventricular Septal Defect

• 1. Craniofacial abnormalities
• 2. Limb defects

• 1. Ethosuxamide
• 2. Lamotrigine
• 3. Topiramate
• 4. Phenobarbital

• 1. Phenobarbital
• 2. Primidone
• 3. Phenytoin
• 4. Carbamazapine

Failing three adequate trials of antiepileptic medications

Rolandic Epilepsy

• Children ages 5-9
• Usually boys

• Begins between ages 5-9
• Remits by puberty

• Unilateral parethesia
• Facial movements
• Speech arrest

"Rolandic spikes" during sleep: high voltage spikes in the temporal region

No!

• Begin between ages 4-10
• 2/3 Remit in early adulthood, rest evolve into tonic-clonic seizure disorder

2-10 seconds

3Hz spike-and-wave complexes in all channels

None

Abrupt cessation of antiepileptic medications in a patient with history of absence seizures

Occasional, asymmetric bursts of 3Hz spike-and-wave complexes lasting 1-1.5 seconds

• Blinking
• Facial and finger automatisms
• Subtle clonic limb movements

• 1. Ethosuxamide (first line)
• 2. Valproate

• Usually none
• If present, malaise or depression

• Lose consciousness
• Roll eyes upward
• Extend back, trunk, and limbs (forms a back-bending arch)
• Diaphragm, chest wall, and laryngeal muscles contract, causing the "epileptic cry"
• Bite tongue
• Lose continence

• Spikes, polyspikes, and occasional slow waves in all channels
• Typically obscured by muscle artifact

Bursts of generalized spikes in the background

Prolactin is elevated

Autosomal dominant

Non-REM sleep

• 1. Valproate
• 2. Phenytoin

• Women aged 19-35
• Relatives of people with epilepsy
• People with a history of abuse

Episodic anterograde amnesia with retrograde amnesia for the past several hours/days

• Momentary loss of body tone (30 seconds or less)
• Often occurs during a period of strong emotion
• Awareness is preserved

• 1. Children
• 2. Adults with brain injury

• 1. Lithium (if toxic)
• 2. Tricyclic antidepressants
• 3. Clozapine

Levitiracetam (Keppra)

• 1. Obesity
• 2. Hair thinning
• 3. PCOS
• 4. Hyperandrogenism

Phenytoin

• 1. Multiple antidepressant medications
• 2. Complex partial seizures

Causes antiepileptic levels to fall, causing increased seizure frequency

Leviteracetam (Keppra)

Seizure whose sole manifestation is mirthless laughter

• 24 hours is maximum time to be called a TIA
• Most last 30-60 minutes

Platelet emboli

Cerebral hemispheres

• 1. Hemiparesis (contralateral)
• 2. Hemisensory loss (contralateral)
• 3. Homonymous hemianopsia (contralateral)

• Brief monocular blindness (1-5 minutes)
• Caused by TIA originating in the carotid artery affecting the ophthalmic artery

Plaques are present due to retinal emboli

• Internal carotid
• External carotid

• 1. Ophthalmic Artery
• 2. Anterior Cerebral Artery
• 3. Middle Cerebral Artery

• Middle Cerebral Artery
• Everything except the leg!

Middle Cerebral Artery

Middle Cerebral Artery

• Anterior Cerebral Artery
• Perfuses area innervating the leg

Anterior Cerebral Artery

Posterior Cerebral Artery

Posterior Cerebral Artery

Basilar

Platelet inhibitors (aspirin, clopidogrel/Plavix, Dipyiridamole-Aspirin/Aggrenox)

Joining of the two vertebral arteries after they enter the skull

Small branches of the Basilar Artery

Large branches of the Basilar Artery

Left and right Anterior Cerebral Arteries

Internal Carotid and Posterior Cerebral Artery (just as it comes off of the Basilar Artery)

• 1. In the chest, at the origin of the vertebral arteries
• 2. Junction of the vertebral arteries at the base of the brain

• 1. Circumoral tingling
• 2. Dysarthria
• 3. Nystagmus
• 4. Diplopia
• 5. Ataxia
• 6. Vertigo

• TIA stopping all flow through the Basilar Artery causes brainstem ischemia
• Sudden loss of consciousness and tone causes the patient to collapse

TIA of the PCA, affecting the hippocampus

3-24 hours total, most severe for 1-2 hours

Risk is elevated, but only somewhat so

Risk is elevated, but only somewhat so

Crack cocaine

• Marfan-like body habitus
• Ocular lens displacement
• Strokes in childhood

• Embolic strokes occur suddenly
• Strokes caused by thrombus develop slowly or intermittently

Day 3-5

• 1. Contralateral lower extremity paresis
• 2. Mutism, apathy
• 3. Pseudobulbar palsy, if bilateral
• 4. Personality changes, if bilateral
• 5. Urinary incontinence, if bilateral

• 1. Contralateral hemiparesis
• 2. Hemisensory loss
• 3. Aphasia
• 4. Hemi-inattention

• 1. Contralateral homonymous hemianopsia
• 2. Alexia without agraphia
• 3. Cortical blindness, if bilateral

• 1. Coma
• 2. Locked-in Syndrome

• 1. Cranial nerve palsy
• 2. Contralateral hemiparesis
• 3. Internuclear ophtalmoplegia

Lateral Medullary (Wallenberg) syndrome

• Fourth ventricle and medulla are compressed:
• Compression of fourth ventricle causes obstructive hydrocephalus
• Compression of medulla depresses respiratory drive and causes coma

• 1. Basal ganglia
• 2. Thalamus
• 3. Pons
• 4. Cerebellum

Likely due to HTN triggered by consumption of aged cheese or red wine, or taking meperidine (Demerol)

Subarachnoid Hemorrhage

• Most remit after 1 year
• 20% remain depressed at 3 years

• All motor function, except extraocular muscle and eyelids, is lost
• Require tracheostomy and ventilator support, as well as feeding tube
• Cognition and decision making capacity are intact

Extensive cortical damage without brainstem damage

Decorticate

PET and fMRI show generalized markedly reduced cerebral blood flow and glucose metabolism

1 month

1 year

3 months

Brain injury impairs level of consciousness, but some discernible behavioral evidence of consciousness is present

Some organized cerebral cortical activity is present

14 days

Topamax

"Farsightedness"

Myopia

Hyperopia

Lens thickness and pupil size adjustment to facilitate focusing of an image on the retina

• 1. SSRIs
• 2. SNRIs
• 3. TCAs
• 4. Clozaril

Phenothiazines

• 1. Digoxin (if toxic)
• 2. Viagra

Viagra

Vigabatrin (Sabril)

The Optic Disc

Segment of the optic nerve behind the eye

• Sudden Vision loss
• Color desaturation
• Pain on eye movement

• 1. Multiple Sclerosis
• 2. Neuromyelitis Optica
• (Demyelinating illnesses)

Multiple Sclerosis

Atrophy of the optic nerve, causing blindness and unreactive pupil

Steroids

Atrophy of the optic nerves

• 1. Headache
• 2. Malaise
• 3. Aches/pains
• 4. Optic nerve ischemia

• Visual loss in one eye, then the other several months later
• No other CNS or musculature symptoms

Mostly young males

• 1. Cognitive decline
• 2. Personality changes
• 3. Blindness
• 4. Death by age 5 in most cases

• Compresses optic nerve, frontal, and temporal lobe:
• 1. Partial seizures
• 2. Cognitive decline
• 3. Personality changes
• 4. Optic atrophy causing unilateral blindness

• Eye is red
• Pupil is dilated and unreactive
• Eye and forehead are painful

Tricyclic antidepressants

Posterior α-rhythm is lost

Recurrent visual images ("echos") in an area of incomplete visual loss

Both occipital and parietal lobes

Inability to appreciate the meaning of an object despite being able to see it clearly

• 1. Multiple small strokes
• 2. Alzheimer Disease
• 3. Klüver-Bucy syndrome

Inability to name colors, despite being able to see colors (can identify when items are the same or different colors, etc)

Inability to recognize that a face is a familiar person

• 1. Bilateral frontotemporal lobes
• 2. Right temporal lobe

Nondominant cerebral hemisphere

• 1. Ocular Apraxia
• 2. Optic Ataxia
• 3. Simultagnosia

Bilateral parietal-occipital region

Inability to look away from an object once fixated on it

Inability to look/search with the eyes in a deliberate pattern

• Inability to attend to objects that are not in the center of the visual field
• Can describe elements of a scene, but not the overall picture

Hallucination when falling asleep

Hallucination when awakening

Early in the course

Late in the course

• Oval or kidney-shaped
• Crosses the midline

Contralateral hemianopsia

Contralateral hemianopsia

Contralateral temporal lobe (can be associated with a seizure focus!)

Contralateral occipital lobe lesion

Move through the temporal lobe's anterior tip, then posteriorly through the temporal lobe to the occipital cortex

• Supranuclear centers are in the cortex, and innervate nuclear centers
• Nuclear centers are in the pons, and innervates cranial nerve nuclei

Nuclear centers (in pons)

Nuclear centers (in pons)

• The contralateral side
• (think of each gaze center as "pushing" the eyes away)

• Away from the side with seizure activity
• Occurs because the seizure triggers the cerebral gaze center

• Toward the side where the stroke is
• Occurs because that side's cerebral gaze center's activity is reduced or abolished

Cortex!

Corticobulbar tracts

Pontine gaze center

• The ipsilateral side
• (think of each gaze center as "pulling" the eyes in)

Pons!

• 1. Ipsilateral Abducens Nucleus
• 2. Contralateral Oculomotor Nucleus (via Medial Longitudinal Fasciculus)

• Inability of ipsilateral eye to adduct past midline
• Lesion is in Medial Longitudinal Fasciculus

• 1. Phenobarbital
• 2. Dilantin/Phenytoin

Inner ear

Saccades are abnormal

Abnormal smooth pursuit

The affected eye

Either eye

• 1. Brainstem
• 2. CN3, CN4, or CN6
• 3. Neuromuscular junction
• 4. Extraocular muscles

• 1. Oculomotor (CN3)
• 2. Abducens (CN6)

Oculomotor (CN3)

Pupil is not affected

Abducens (CN6)

Loss of vision in an eye with strabismus

The unaffected eye

Mitochondrial myopathy

Downward and inward

• 1. Ptosis
• 2. Miosis (constricted pupil)
• 3. Anydrosis (lack of sweating) unilaterally

Hypothalamus

• Descends from hypothalamus into cervical and upper thoracic spinal cord
• Leaves from thoracic spine and makes a hairpin turn, ascending adjacent to cervical spine
• Wrap around common carotid, then internal carotid
• Enter the orbit with CNV, branch V1

Benign deprivation of parasympathetic innervation to a pupil causes dilation at rest and brisk, long-acting constriction with cholinergic drops

• 1. Small pupil (miosis)
• 2. Ptosis
• 3. Irregular shape
• 4. Does not react to light
• 5. Does react during accommodation

Cause accommodation paresis

Multiple Sclerosis

Retinitis Pigmentosa

Temporal lobe

Temporal lobe

Temporal lobe

Vestibular nuclei of the pons

Phenothiazines (eg Thorazine, Prolixin)

Bilateral temporal lobes

Paresis of all extraocular muscles, causing eye immobility and ptosis

Methanol poisoning

Periventricular leukomalacia (damage to white matter around lateral ventricles)

Less than 4 at 10 and 15 minutes

Cerebral Palsy

• 1. Spastic
• 2. Extrapyramidal
• 3. Mixed

4 months

• 1. Diplegic
• 2. Hemiplegic
• 3. Quadriplegic

Growth arrest causes affected limbs to be short and to have short Achilles Tendons that force the patient to walk on their toes

Spastic symptoms of bilateral legs more than arms

Intellectual disability and epilepsy are uncommon

Spastic symptoms of one side of the body, face and arm more than leg

Paresis in the other hand due to Hemiplegic Cerebral Palsy

None! The unaffected hemisphere will become the dominant language hemisphere

• Spastic symptoms of all four limbs
• Often accompanied by pseudobulbar palsy

Intellectual disability and epilepsy are very common

• 1. Athetosis of the face, tongue, hands, and feet
• 2. Chorea of the trunk, arms, and legs
• (Termed "choreoathetosis")

Dopamine-Responsive Dystonia is progressive, diurnal, and improves with levodopa

Hearing impairment (auditory pathways are often damaged in addition to basal ganglia)

Basal Ganglia

Age 2-4

Very low!

Both spastic paraparesis and choreoathetosis are present

Very high (95%)

The medulla and the lower portion of cerebellum protrude below the foramen magnum

• Posterior brain structures do not form beyond early embryonic stage
• 4th ventricle becomes a large cystic structure

• 1. Headaches
• 2. Bulbar palsy
• 3. Neck pain

Aqueductal stenosis causes obstructive hydrocephalus

• Lumbar vertebrae do not fuse, but underlying spinal cord and cauda equina are intact
• Asymptomatic

• Form of spina bifida
• Meninges and skin protrude through a lumbosacral spine defect

• 1. Leg weakness/gait impairment
• 2. Neurogenic bladder

• Severe form of spina bifida
• Rudimentary lower spinal cord, as well as lumbar and sacral nerve roots, protrude into the sac overlying the lumbosacral spine

• 1. Flaccid Paraparesis
• 2. Areflexia of lower limbs
• 3. Incontinence

Autosomal dominant

• 1. Facial angiofibromas: smooth, firm nodules in the malar region; appear in adolescence
• 2. Hypopigmented macules (ash-leaf spots)
• 3. Shagreen patches: leathery, scaly areas on trunk/buttocks
• 4. Periungual fibromas of the fingers

• 1. Epilepsy (often refractory)
• 2. Intellectual disability
• 3. Facial angiofibroma

• 1. Angelman Syndrome
• 2. Fragile X
• 3. Klinefelter Syndrome
• 4. Rett Syndrome
• 5. Tuberous Sclerosis

"Tubers": 1-3cm nodules that irritate cortex, causing epilepsy and intellectual impairment

• 1. Brain
• 2. Retina
• 3. Kidney
• 4. Heart

• 1. Café-au-lait spots
• 2. Neurofibromas
• 3. Lisch nodules

• Uniformly light brown, oval, flat skin
• May be accompanied by freckles in the axilla or groin

6 or more, each larger than 5mm in children or 1.5mm in adults

• Soft, palpable subcutaneous growth on a peripheral nerve or nerve root
• A few millimeters to several centimeters in size

Multiple pigmented aggregations on the iris of the eye

Optic glioma

Bilateral acoustic neuromas

• 1. Acoustic neuroma
• 2. Meningioma

Angioma of the face (follows one or more branches of CN5) and underlying cerebral hemisphere

• 1. Seizures (of any type) often refractory to medications
• 2. Learning disabilities (can have intellectual disability)
• 3. Focal neurologic symptoms related to location of cerebral angioma (sometimes)

Small, dilated vessels (telangiectasias) on the conjunctiva, bridge of nose, and cheeks

Degeneration of the cerebellar vermis

• Ataxia first occurs between ages 3-5 and is progressive
• Typically wheelchair-bound by age 12
• Eventually, cognitive impairment occurs

Autosomal recessive

Immunodeficiency (both cellular and IgA/IgE deficiency)

Hepatic phenalalynine hydroxylase

• 1. Growth restriction
• 2. Lack of pigment (hair, eyes, skin)
• 3. Eczema
• 4. Malodorous urine
• 5. Cognitive impairment with language delay

Autosomal recessive

• 1. Short stature
• 2. Anemia
• 3. Hypoglycemia

17

22

11

12

21

• 1. Homocystinuria
• 2. B12 deficiency
• 3. Some antiepileptic medications (Carbamazapine, Phenytoin)
• 4. Nitrous oxide

• 1. Vascular thrombotic events (strokes in young adults)
• 2. Mental retardation
• 3. Behavioral disturbances
• 4. Obsessive-compulsive symptoms

• 1. Ocular lens is displaced
• 2. Tall, Marfan-like stature
• 3. Sunken or bowed chest

Supplement Vitamin B6 and Folate

15

15

Always either paternal inheritance or a de novo mutation

• 1. Intellectual disabililty
• 2. Behavior problems
• 3. Hyperphagia, causing obesity

• 1. Obesity
• 2. Short statue
• 3. Small hands and feet
• 4. Small penis/testicles or labia

Usually maternal inheritance

• 1. Severe intellectual impairment with prominent language deficiency
• 2. Epilepsy
• 3. Stereotypies
• 4. Ataxic movements
• 5. Smiling face
• 6. Unprovoked laughter

7

• 1. Broad forehead
• 2. Prominent cheeks
• 3. Flat nasal bridge
• 4. Large, upturned nostrils
• 5. Hypoplastic, widely-spaced teeth
• "Elfin"

• 1. Slow to acquire motor milestones
• 2. Poor visuospatial sense
• 3. ADHD, phobias, or both
• 4. Mild to moderate intellectual disability
• 5. One-sided but "bubbly" conversations ("hypersocial")

22

• 1. Soft palate (cleft)
• 2. Heart (VSD, abnormal aorta and pumonary artery)
• 3. Face (elongated with micrognathia, tubular nose, deformed ears)

• 1. Low IQ
• 2. Schizophrenia
• 3. Major Depression

• Boys nearly always have physical signs, and 70% have significant intellectual disability
• Girls largely have no physical signs, and 2/3 have normal IQ

• 1. Stereotypies (especially hand wringing or flapping)
• 2. Self-injurious behavior

• 1. Autism
• 2. ADHD
• 3. Anxiety

• Trinucleotide repeats in the X chromosome
• Must have 200 repeats to have the disorder

6-18 months

Regression over a period of several years; eventually unable to walk or produce language

Epilepsy beginning around age 3

• 1. Stereotypies, especially hand wringing/clapping/flapping and hair pulling
• 2. Microcephaly

X

Essentially entirely female; the mutation is letal to a male fetus

X

• 1. Intellectual disability
• 2. Self-mutilation
• 3. Dystonia (prominent)

Essentially all male

• Most have learning disabilities
• 10-20% have Intellectual Disability

• Short statue
• Webbed neck
• Low set ears
• Flat nose
• Do not undergo puberty

• Tall, mostly due to long legs
• Few secondary sexual characteristics (do not go through puberty)
• Gynecomastia
• Female pattern of pubic hair
• Small testes

• 25% have intellectual disability
• Most have below average IQ

• 1. Learning disabilities
• 2. Meet milestones late
• 3. IQ lower than siblings

Aortic stenosis

• 1. Large ears
• 2. Macro-orchidism
• 3. Narrow ears
• 4. Short stature
• 5. Arched palate
• 6. Hyper-extendible joints

Cavitations within the brain

Rett Syndrome

Substantia gelatinosa

Substance P

• 1. Lateral spinothalamic tract (predominant tract)
• 2. Spinohypothalamic tract
• 3. Less-defined tracts to limbic system and brainstem

• Originate in frontal lobe and hypothalamus
• Project to periaqueductal gray matter

Interneurons release endogenous opioids

• Originate in brainstem
• Descend in the dorsolateral funiculus of the spinal cord

Serotonin

Regular prophylactic dosing rather than taking medication when pain begins

Opiates

• 1. Topical lidocaine
• 2. Gabapentin
• 3. Pregabalin
• 4. Carbamazepine
• 5. Oxcarbazepine

Intercostobrachial Nerve

Metastatic invasion of the brachial plexus

• 1. Thoracic dermatomes
• 2. First branch of Trigenimal Nerve (CNV1), including the cornea

Opioids!

Postherpetic neuralgia lasting 3-6 months

• Type 1: No definable underlying nerve injury
• Type 2: There is a definable underlying nerve injury

CRPS/RSD

• Initially, contralateral hemianesthesia
• Over time, spontaneous painful sensations on the anesthetic side of the body (lasts 6-12 months)

3rd and 4th ventricles

Substantia Gelatinosa

Pain caused by loss of sensation from a body region (eg phantom limb pain)

Obsession with obtaining a pain medication, followed by hoarding the medication

Diabetic neuropathy

T10-L1

• T-cell mediated inflammation leads to demyelination and sclerotic plaques in the white matter
• Axonal death leads to permanent dysfunction

Once every 1-2 years

• 1. Relapsing-remitting (most common)
• 2. Primary progressive
• 3. Secondary progressive (initially relapsing-remitting, then progressive)
• 4. Progressive-relapsing (steady deterioration with superimposed acute attacks)

40s-50s (older than other forms)

Spinal cord

Cerebellum

Irregular head tremor in cerebellar damage

Vibration and position sense

• Optic nerve is often affected (due to CNS myelin)
• Acoustic nerve is rarely affected (partially covered with CNS myelin)
• Others are never affected

Optic neuritis causes scotoma and color desaturation, as well as pain on eye movement

When a flashlight is swung from the normal eye to the affected eye, both pupils dilate

• Internuclear ophthalmoplegia
• Nystagmus

• 1. Incontinence (neurogenic bladder)
• 2. Impotence
• 3. Impaired gait (leg spasms)

• Men have low sperm count and abnormal sperm production
• Women's fertility is not affected

• Electrical sensations down the spine on neck flexion
• Indicates a disease process affecting the cervical spine

• Risk of exacerbations is much lower than normal during pregnancy and while breastfeeding
• 2-3 months after birth, incidence of exacerbation is increased

Major Depression

• SSRIs are not effective
• ECT is effective and is not contraindicated or restricted

• Over the course of disease, memory declines, eventually causing cortical dementia
• Language is spared

• 1. Enlarged ventricles
• 2. Atrophy of corpus callosum
• 3. Demyelination of periventricular white mater
• 4. High overall lesion load

• Nearly always relapsing-remitting at onset
• Often evolves into secondary progressive pattern after decades

1 gadolinium-enhancing lesion OR 9 nonenhancing lesions

Lesions that arose in the past month are enhancing; older lesions are not

• Normal or slightly-elevated protein
• Oligoclonal bands are frequently present, but nonspecific
• Myelin basic protein is frequently present, but nonspecific

Alpha-interferon (used for hepatitis)

Guillain-Barré consists of a single attack, and is symmetric

• Loss of vision in one or both eyes
• Paraparesis

Demyelinating lesions in one or both optic nerves, as well as the spinal cord

NMO does not cause cognitive impairment or fatigue

• 1. Plasmapheresis
• 2. Immunosuppressants

• Leukodystrophy usually first appears in childhood, and is progressive and unremitting
• Leukodystrophy is entirely genetic in etiology

Sex-linked

Neurologic problems and adrenal insufficiency in boys starting between ages 5 and 15

• 1. Gait impairment
• 2. Mania
• 3. Dementia

Peripheral neuropathy

Oxidation defect in peroxisomes cause accumulation of fatty acids, leading to demyelination

Immune attack on CNS myelin 1-4 weeks after an infectious illness (often one with a skin eruption)

Caribbean

• Contaminant of Italian red wine causes degeneration of corpus callosum
• Causes frontal lobe damage and dementia

• Inflammatory demyelination 1-2 weeks after smallpox vaccination
• Rare, but if it occurs mortality rate is high!

Serum NMO antibody

• 1. Multiple Sclerosis
• 2. Labyrinthitis
• 3. Wernicke's Encephalopathy

• 1. Seizures
• 2. Strokes
• 3. Psychosis
• "The 3 S's"

Pudendal nerve

T11-L2

S2-S4

If central, DTRs will be hyperactive. If peripheral, hypoactive

Sympathetic! (parasympathetic causes relaxation)

S3-S4

• 1. Diabetic neuropathy
• 2. Spinal cord injury
• 3. Multiple sclerosis
• 4. Herniated disc

Autonomic injury

Applying a cold surface to the scrotum causes ipsilateral skin contraction and testicle retraction

Stroking the inner thigh causes ipsilateral scrotal skin contraction and testicle retraction

Scratching the skin surrounding the anus causes the anus to tighten

Yohimbine (alpha antagonist that increases sympathetic activity)

• 1. Alprostadil
• 2. Papaverine
• 2. Phentolamine

-afil

• As the genital-spinal cord loop is intact, can achieve orgasm (but can not perceive it)
• Erections are often weak
• Sperm count is low (may become infertile)
• Can have autonomic hyperreflexia with an orgasm

Can not achieve orgasm

Dopamine

• 1. Delayed orgasm
• 2. Erectile dysfunction (1/3)
• 3. Reduced vaginal lubrication

• 1. Wellbutrin
• 2. Trazodone

• 1. Clomipramine
• 2. Sertraline

• Alpha adrenergic blockade
• (Rare side effect!)

Inject epinephrine into the penis

• Damage to bilateral amygdala
• Aggressive/sexually suggestive gestures
• Eat, drink, and smoke excessively
• Amnesia

• 1. Hippocampus and adjacent amygdala
• 2. Fornix
• 3. Mamillary bodies
• 4. Mammillothalamic tract
• 5. Thalamus (anterior nucleus)
• 6. Cingulate gyrus

• Flaccid paralysis
• Areflexic

• Repositioning every 15-20 minutes
• Tone is intact

Slow, rolling movements

Either slow, rolling movements or no movements

None

Slowed alpha activity

• Low amplitude
• Sleep spindles and/or K complexes present

• Delta activity
• Sleep spindles

• Similar to that of wakefulness
• Ocular movement artifact

• Increased
• Pulse, blood pressure, intracranial pressure, and intracranial blood flow increase

Pons

Abolishes muscle tone

• 1. Dopamine
• 2. Epinephrine
• 3. Norepinephrine
• 4. Serotonin

• 1. ↑ cholinergic activity
• 2. ↓ monoamine activity

Suppress REM activity

• Reduced
• Causes hypotension, bradycardia, and cerebral blood flow

• 1. Growth hormone
• 2. Prolactin

Early in the sleep cycle

Time to fall asleep after going to bed

Adenosine

Ratio of sleep to time spent in bed

• 4-5 times per night
• First episode is 90-120 minutes after falling asleep
• Longer and more frequent in the latter half of the night

Suprachiasmatic nucleus of the hypothalamus

• 1. Depression
• 2. Narcolepsy
• 3. Sleep apnea
• 4. Sleep deprivation
• 5. Withdrawal from alcohol/hypnotics/TCAs

Suprachiasmatic nucleus

Darkness

Melatonin agonist with longer half-life than melatonin itself

Luvox inhibits metabolism of Ramelteon, causing elevated levels

• Short sleep latency
• Increased sleep time
• Greater depth and duration of slow-wave sleep

"REM Rebound" with dreaming nearly immediately after falling asleep, more REM cycles, and longer REM cycles

• 1. SSRIs
• 2. TCAs

• 1. Cocaine
• 2. Amphetamines
• 3. Opioids
• 4. Hypnotics
• 5. Alcohol

REM occurs at high frequency in infancy, reducing in percentage of the night until age 5, then constant into adulthood

• Between adolescence and 30s
• Peaks in teenage years

~15 minutes

• 1. Excessive Daytime Sleepiness
• 2. Cataplexy (not always present)
• 3. Sleep Paralysis
• 4. Hypnagognic/hypnopompic hallucinations

• Inability to move or speak for as long as several minutes on awakening
• Can move eyes and breathe

Multiple brief spontaneous awakenings occur

• Develop inattention and hyperactivity
• Behavioral, cognitive, and scholastic impairments due to fatigue
• Often mistaken for a learning disability

Multiple Sleep Latency Test (MSLT)

Excitatory neurotransmitter that maintains wakefulness and stimulates appetite

• Histaminergic (non-amphetamine) medication that promotes wakefulness
• Does not cause excitation or nighttime insomnia

• Long-acting form or Modafinil (Provigil)
• Promotes wakefulness, but is not an amphetamine

• Regular daytime naps after meals and during late afternoon
• Regular nighttime sleep schedule
• Stimulant medication

• 1. Obstructive
• 2. Central (due to inconsistent CNS ventilatory effort)

Enlarged tonsils

After 45

Iron deficiency anemia

Dopamine agonists (eg L-dopa, ropinirole, and pramipexole)

• Dopamine agonist
• Not an ergot derivative

• Dopamine agonist
• Not an ergot derivative

• 1. TCAs
• 2. SSRIs
• 3. SNRIs
• 4. Antihistamines

Regular episodic stereotyped movements of limbs (usually legs) during sleep

• 20-40 second movements for episodes of 10 minutes to several hours
• Occur during NREM sleep
• Does not arouse the patient

• 1. Uremia
• 2. Anemia

• Usually none!
• If necessary, benzodiazepines and dopaminergic medications

• "Periodic hypersomnia" of 1-4 weeks of 18 hours of sleep per day occurring 3-4 times per year
• After awakening, eat voluminous amounts of food, are crudely sexual, and are confused

• First occurs in adolescence
• Spontaneously resolves after about 8 years

• No physical findings can confirm the diagnosis
• No specific treatments exist; must treat symptoms

Inhibits metabolism of medications

Inhibits metabolism of caffeine, causing increased levels

Mental or behavioral aberrations lasting 15 minutes or less that interrupt sleep

NREM sleep, most often stage IV sleep in early night

NREM sleep, most often stage IV sleep in early night

• 1. Falling rapidly into deep sleep (overtired, hypnotic medications, etc)
• 2. Being partially awakened (need to urinate, loud noises at night, etc)

• Disorentation and incoherence when partially, rather than fully, awakening from sleep.
• Causes "talking in one's sleep"

10 minutes

1-10 minutes

• Begins in adolescence
• Regresses in the 5th decade
• More common in men

• Stereotyped movements while in the early stages of falling asleep
• Starts in infancy, resolves by age 5 in most but can persist into teens (particularly if intellectually disabled)

In REM rebound (including use of drugs or withdrawal from REM-suppressing medications)

• Occur in NREM sleep
• Awaken able to recall the fear, but not any associated imagery

Lack of paralysis during REM sleep

• Those with REM Sleep Behavior Disorder remember the episodes (thought they are associated with dreams)
• Those with NREM Parasomnias are amnestic of their episodes

Men older than 65

• 1. Parkinson disease
• 2. Lewy Body Dementia

• 1. SSRIs
• 2. SNRIs
• 3. TCAs
• 4. Mirtazapine

Clonazepam taken at night

After age 5

After age 6

• Usually during NREM sleep, but not exclusively
• Lasts about 5 minutes

• While partially aroused from sleep, eat variable amounts of food
• Food may be barely edible, eg raw meats or still-frozen foods

Awaken fully from sleep, consume large amounts of their customary foods, then return to sleep

• Reduced total sleep efficiency
• Slow wave sleep is relatively reduced, and is fragmented

Very short; nearly always less than 60 minutes

Increased in early nighttime; almost absent in later sleep

• 1. Earlier cortisol release
• 2. Earlier MHPG (norepinephrine metabolite) release

Nearly abolished

• 1. SSRIs
• 2. SNRIs
• 3. TCAs
• 4. MAOIs
• 5. Benzodiazepines
• 6. Amphetamines
• 7. Lithium

Polysomnography shows normal results

• 1. Reduced slow wave sleep
• 2. Increased sleep latency with frequent awakenings

• 1. Increased sleep latency
• 2. Fragmented sleep
• REM sleep is normal

None! (psychologic >> physiologic sleep problems!)

• 1. Shortened sleep latency
• 2. Increased slow-wave sleep
• 3. Decreased REM sleep in the first half of sleep, with rebound in the second half of sleep
• 4. Periods of wakefulness

• 1. Increased sleep latency
• 2. REM rebound

• Increased light sleep
• Decreased sleep efficiency
• Many daytime naps

• 1. Frightening vivid dreams
• 2. Can cause sleep attacks (episodic irresistible sleep)

• 1. Causes REM Sleep Behavior Disorder
• 2. Sleep reversal (sleep during day, up at night)
• 3. Fragmented sleep

TCAs

• 1. Tremors
• 2. Athetosis
• 3. Chorea

Sudden contraction of antigravity muscles during wake-to-sleep transition

• 1. Dystonia
• 2. Tics
• 3. Belpharospasm
• 4. Hemifacial spasm

• Hereditary prion disease
• Symptoms begin at age 50
• Progressively severe insomnia, inattentiveness, and amnesia
• Eventually, endocrine and ALS-like symptoms
• Death in 6-36 months

N1 and N2

• Generalized seizures
• Partial seizures are much less common

• Promote normal sleep
• Can cause daytime sleepiness despite normal sleep

REM sleep

During the hours just before awakening

If unable to fall asleep within 20 minutes, leave bed and read until relaxed and sleepy

Can precipitate serotonin syndrome

• 1. Increase sleep time by 10%
• 2. Decrease slow-wave and REM sleep

Pons

None! (most resolves on its own)

Sleep Onset REM Period (eg REM immediately after falling asleep)

• 1. Sleep Apnea
• 2. Narcolepsy
• 3. Sleep deprivation

Mild anticonvulsant effect

• 1. TCAs
• 2. Sodium oxybate (GHB)

Dopamine agonist

Dopamine agonist

250mg

• 1. Parkinson disease
• 2. Athetosis
• 3. Chorea
• 4. Hemiballismus
• 5. Wilson Disease
• 6. Generalized dystonia

• 1. Globus pallidus
• 2. Putamen

Posterior Internal Capsule

• 1. Dopaminergic neurons from substantia nigra project to Putamen
• 2. Putamen projects to Globus Pallidus
• 3. Globus pallidus projects to Ventrolateral Nucleus of the thalamus
• 4. Ventrolateral nucleus projects to motor cortex
• 5. Motor cortex projects back to Putamen

• 1. Caudate
• 2. Putamen
• 3. Globus Pallidus
• 4. Subthalamic Nucleus
• 5. Substantia Nigra

Basal ganglia

Modulates the corticospinal tract

Nigrostriatal tract

Substantia Nigra and Striatum

Dopamine

GABA

Glutamate

Contralateral side!

Increases involuntary movements

Loss of postural reflexes

• Taking steps back when pulled from the shoulders
• Sign of loss of postural reflexes in movement disorders

Anosmia

• 1. Urinary incontinence
• 2. Constipation
• 3. Dysphagia
• 4. Diaphuresis

After the Parkinson regimen is optimized

TCAs

• Selegiline prevents breakdown of serotonin at high doses
• Combined with reduced reuptake of serotonin, this can precipitate serotonin syndrome

• Yes!
• Helps depression, as well as bradykinesia and rigidity

None; antidepressants must also be given

Begins to occur approximately 5 years after onset of illness

Akinesia and rigidity

Inattention, slowed thinking, poor memory, and hallucinations

None

In Lewy Body Dementia, dementia is the presenting symptom, whereas in Parkinson Disease it develops later

Cholinesterase inhibitors

High rate of dementia and death within 2 years

• Taper cholinergic medications, if possible
• Add antipsychotic medication

Clozapine

• Psychiatric illness that occurs in Parkinson Disease due to dopaminergic medications
• Compulsive self-gratifying behavior (gambling, sex, buying, or binge-eating)

• Reduce dopamine agonists
• Deep brain stimulation

• Mindless, repetitive, purposeless behavior that displaces normal activities
• Caused by dopaminergic medications

• Reduce dopaminergic medications
• Add an antipsychotic

• 1. Phenylalanine converted to Tyrosine
• 2. Tyrosine converted to DOPA (by tyrosine hydroxylase) (rate determining step)
• 3. DOPA converted to Dopamine (by DOPA decarboxylase)

Inabilitly to convert Tyrosine to DOPA to synthesize Dopamine

Nigrostriatal Tract

Serotonin

Loss of pigmentation in substantia nigra, locus ceruleus, and vagus nuclei in the brainstem

Parkinson Disease

Intellectual deterioration and bradykinesia due to repeated head injuries (eg in boxers)

Parkinsonism

Parkinsonism

Parkinsonism

Parkinsonism

Parkinsonism

• Typically several weeks
• In some cases, 3-12 months

• Stop the offending medication
• Amantadine can be given temporarily (stop after 3 months to see if it is necessary!)
• Do not give dopaminergic medications!

• Similar to Parkinson Disease, but due to loss of postsynaptic dopamine receptors rather than dopaminergic neurons
• Does not respond to dopaminergic medications

Approximately first 5 years of illness

• Reduces metabolism of L-Dopa to dopamine by DOPA decarboxylase
• Does not cross blood-brain barrier, so prevents systemic side effects of L-Dopa

• 1. Nausea/vomiting (stimulates emesis center of brain)
• 2. Hypotension
• 3. Arrhythmia

• Inhibits breakdown of dopamine at usual doses (blocks MAO-B)
• At high doses, blocks MAO-A, which increases serotonin and catecholamine levels
• Breakdown products are similar to amphetamines and cause activation

Dopamine agonists

Dopamine agonist

Dopamine agonist

• Injectable dopamine agonist
• Used in severe Parkinson Disease or NMS

Treat only rigidity and bradykinesia, not other symptoms

• 1. Psychotic symptoms (hallucinations, thought disorder)
• 2. Movement disorders (chorea, akithesia, dystonia)

• 1. Face
• 2. Neck
• 3. Distal limns

Cerebral palsy confined to the Basal Ganglia

Dopamine antagonist

• 1. Cocaine
• 2. Amphetamine
• 3. Methylphenidate

Estrogen

• 1. Chorea
• 2. Behavioral disturbances
• 3. Dementia

Late 30s

10-20 years

Random, nonstereotyped, rapid jerking movement of the pelvis, trunk, and limbs

• Inability to sustain voluntary muscle contraction
• Sign of chorea

• Occurs in half of patients
• Begins early in the illness, sometimes before other symptoms

• 1. Antipsychotics (anti-dopamine)
• 2. Tetrabenazine (dopamine depleting)

Depletes dopamine (predominantly), serotonin, and norepinephrine

• 1. SSRIs
• 2. TCAs

Rigidity, dystonia, and akethesia are the presenting symptoms

Juvenile form does, but adult form does not

Chromosome 4 (short arm)

• 35-39 cause mild symptoms, but not the full disease
• 40 or more cause the disease
• 60 or more cause the Juvenile disease

Father

• Striatum, particularly the caudate
• GABAergic neurons are lost

Caudate is atrophied, causing lateral ventricles to balloon outward ("bat wing ventricles")

Hypometabolism in the caudate

• 1. Wilson disease
• 2. Juvenile Huntington Disease
• 3. Drug abuse

Syndenham Chorea caused by rheumatic fever

• Children ages 5-15
• Mainly boys

Complication of rheumatic fever

• Occurs during or several months after Rheumatic Fever
• Lasts ~2 months

• 1. ADHD
• 2. Syndenham Chorea
• 3. Tics/Tourette's
• 4. Drug use
• 5. Medication side effects
• 6. Withdrawal-Emergent Syndrome

• 1. Valproate
• 2. Dopamine antagonists

Resolves after cessation of OCPs

• 1. Chorea
• 2. Delirium
• 3. Psychosis (sometimes)

Middle Cerebral Artery

Toxoplasmosis lesions in basal ganglia

• Most cases resolve spontaneously
• In persistent cases, dopamine antagonists may help

• 1. Brain
• 2. Liver
• 3. Cornea

Lenticular nuclei

• 1. Personality/behavior changes
• 2. Thought disorder
• 3. Cognitive impairments, culminating in dementia

• 1. Dysarthria
• 2. Dysphagia
• 3. Gait impairment
• 4. Rigidity/dystonia
• 5. Tremor

Wilson Disease

Ceruloplasmin level (low to absent in Wilson Disease)

24-hour urine copper level

• 1. Copper chelating agents
• 2. Avoid copper-containing foods