Inflammation of the meninges; the membrane that covers the brain and spinal cord

1. Paracellular transport after disruption of tight junctions of the BBB

2. Transport within circulating phagocytic cells (monocytes)

3. Transcellular transport within endothelial cell vacuoles

Neonate

Unwell

Fever, Septic

Lethargic/irritable

Apnea

Neurological signs

Rash

1-18 months 

Fever

Lethargic/Irritable

Seizures

Bulging fontanelle

Rash

> 18 months

Fever

Photophobia

Headache

Seizures

Nausea/Vomiting

Stiff neck

Petichial rash

Infection

Intracranial Lesion near the subarachoid space

Recent Seizure

Radiation Therapy-SCC of the ear

Injection of drug into the intrathecal space

Cells: 500-10,000

Neutrophils: > 90%

Glucose: < 40

CSF/Serum Glucose: < 0.6

Protein: > 150

Increased CSF Opening Pressure: > 600mm

Glucose is low because the WBC utilize the glucose

Protein is high because it is a by product bacteria metabolism

Cells: 10-500

Neutrophils: > 50% early, Late < 20%

Lymphocytes predominate late in infection

Glucose: Normal: 45-85

CSF/Serum Glucose: > 0.6

Protein: < 100 (mildly elevated)

Cells: 0-1000

Neutrophils: < 50%

Glucose: Normal: 45-85

CSF/Serum Glucose: > 0.6

Protein: < 100 (Mildly elevated) 

Hearing Loss

Focal neurological deficits

Congnitive Impairment

Amputation

Acute Bacterial Meningitis

Laboratory Testing

CBC: Leukocytosis (neutrophils predominant), Left Shift (Immature Cells)

 Thrombocytopenia-suggests DIC

Blood Cultures are only 50% sensitive

Do not pre-teat with antibiotics prior to lumbar puncture

Latex Agglutination-unreliable

Gram stain/culture

Lactic Acid Level

• Coagulase (-) staphylococci (non- s. aureus)
• Especially in patients with CNS shunts or who have undergone neurological procedures
• S. aureus
• Pseudomonas aeruginosa

• Less severe than bacterial meningitis
• Shorter in duration than bacterial meningitis
• Glucose is usually normal if it is decreased think mumps, choriomeningitis virus
• Gm stain negative
• Negative bacterial culture
• PCR

• Subacute to chronic
• Headache, Fever, Neck stiffness, Lethargy, Confusion, Meningeal signs, Cranial nerve palsies
• Incidence is increasing in developing countries especially in those with high incidence of HIV
• PPD and PCR used for diagnosis
• Gross Appearance: Typically clear
• Opening pressure elevated
• Cell Count: 50-500
• Mean 223
• Differential: Neutrophils early, Lymphocytic
• Protein: Elevated
• Glucose: Deceased
• Aicd Fast smear: 10% positive rate (not recommended)
• Culture usually negative- if positive it requires 6 weeks
• Nucleic Acid Testing: PCR

Meningitis with CSF Eosinophilia

Prof said "Good Test Question"

Parasitic Infection

Malignancy

Multiple Sclerosis

Subarachnoid Hemorrhage

Obstructive Hydrocephalus with shunt

Granulomatous meningitis-fungus or TB

Idiopathic eosinophilic meningitis

Other Infectious Causes:

TB

Treponema Pallidum (neurosyphilis)

Mycoplasma pneumoniae

Fungal

Rocky Mountain Spotted Fever

Subacute Sclerosing Panencephalitis

Lymphocytic choriomeningitis virus

• Chronic
• Cryptococcus neoformis-leading cause in HIV patients
• Coccidoides immitis
• Vasculitis
• Mucor-diabetic ketoacidosis
• Aspergillus
• Parenchymal invasion
• Candida
• Cryptoccus neoformis

• Primarilt viruses
• HSV: Type 1 most common
• West Nile
• Eastern Equine
• Western Equine
• St. Louis
• LaCross

• Toxoplasma gondii: most frequent, primarily encephalitis, AIDS-reactivation of latent infection.  Associated with Cat litter
• Cerebral Malaria: Plasmodium falciparum
• Cysticercosis: Pork as the primary source of protein. Taenia solium eggs ingested; unable to complete life cycle in humans leading to cyst-like lesions throughout the body including the brain
• Naegleeria fowleri (meningoencephalitis): Swimming in warm fresh water during summer months

• Direct extension from a contiguous site such as an infected paranasal sinus, following trauma or by hematogenous spread from another site
• Hematogenous spread: endocarditis or lung abscess
• Infectious agent carried by small blood clos
• Emboli lodge in the capillaries in the brain causing localized hemorrhage and producing sites from infection leading to abscess
• Immunocomptent patients:
• S. aureus
• Viridans streptococci
• Actinomyces
• Anaerobes
• Immunocompromised
• Aspergillus
• Mucor
• Rhizopus
• Trauma Patients:
• Gm (-) bacteria
• S. aureus

Seizures

Tremors

In Newborns

Excessive Startle

Sandifer Syndrome-associated with GERD

Benign neonatal/nocturnal sleep myoclonus- Normal EEG, myoclonus resolved upon awakening

In Children

Cardiac Problems-arrhythmias

Syncope

Stereotypies

Breath holding spell- Normal kids with immature autonomics will become cyanotic and pale after emotional excitment (tantrums).  Ends on inspiration

• Hypoxic ischemic encephalopathy (HIE) is MC cause
• Major cause of long term mortality and morbidity
• Combination of hypoxia and ischemia that results in decreased O₂ to cerebral tissue
• Intrauterine asphyxia-placenta abruptio
• Postnatal respiratory distress
• Cardiac Disease
• Circulatory insufficiency-sepsis, meningitis, PDA
• Infection
• Group B Strep, E. Coli, Listeria, HSV
• Hemorrhage, in-utero stroke, CNS, malformations
• Metabolic Diseases

• Hypoglycemia
• Electrolyte imbalances
• Hypoxia
• Withdrawals

Weakness and Atrophy

Deep Tendon Reflexes are Increased

Babinsky Reflex: Extensor (+)

Tone: Increased, Spastic

NO Fasciculations

Weakness and Atrophy

Deep Tendon Reflexes are Decreased

Babinsky Reflex: Flexor (-)

Tone: Decreased

Fasciculations Present

• Observe
• Atrophy/Hypertrophy
• Fasciculations
• Changes in function
• Palpate for muscle texture, tenderness
• Examin joint contractures, myotonia, strength, deep tendon reflexes

• Decreased muscles tone → floppy babies
• Central/Cerebral Hypotonia
• Increased deep tendon reflexes, (+) Babinsky, decreased tone
• Genetic Diseases
• Prader Willi (Chromosome 15 paternal deletion)
• Trisomy 13, 18, 21
• Anterior Horn Cell Disease
• Spinal muscular atrophy-failure of survival neuron factor gene
• Chromosome 5
• Type 1 Werdnig-Hoffman (infantile onset)
• Congenital Hypomyelinating neuropathy
• Charcot-Marie Tooth
• Inherited disorder presenting with lower extremity weakness, foot drop, ataxic gait
• Damage to myelin sheath
• Congenital myasthenia gravis-underlying genetic disorder
• Botulism-honey and canned foods, hypotonia, constipation, ileus, and poorly reactive and dilated pupils
• Aminoglycoside toxicity
• Congenital muscular dystrophy
• Congenital myopathies- Nemaline rod, Central core

Cerebral Palsy

CP

• Non-degenerative motor encephalopathy due to injury early in neuro-development
• Prenatal injury is MC
• TORCH, genetics, drugs, alcohol, placental insufficiency
• Perinatal-trauma, HIE
• Post-natal- infection, trauma
• Spastic CP
• MC
• 75%
• Quadriplegia-can't/don't walk
• Diplegia/Paraplegic
• Can be caused by Paracventricular leukomalacia (PVL)
• Both legs affected but mostly normal upper extremities
• Child may develop contractures of ankles and feet
• Often seen in premature babies
• Hemiplegia from MCA infarct
• Arm bent, hand spastic or floppy, often of little use
• Child will walk on tiptoes or outside of foot on affected side
• Unaffected side is completely or almost normal
• Dystonic CP-basal ganglia damage
• Kernicterus
• Ataxic CP-Cerebellar damage
• Balance and coordination difficulties than increased tone
• Hypotonic CP
• Mixed CP
• Complications:
• Seizures
• MR
• Spasticity
• Contractures
• Scoliosis
• Hydrocephalus
• Bowel/bladder involvement

• MC cause of CP in developing countries
• Occurs when unbound/free bilirubin extraction is too high and bilirubin is deposited in the basal ganglia and hippocampus
• Presents with hypotonia, lethargy, poor feeding, and fever
• At 2nd month of life infant develops extrapyramidal symptoms (chorea, tremor, dystonia)
• Treatment is phototherapy and exchange transfusion

• Migraine with or without aura
• Nausea/emesis
• Photophobia
• Phonophobia
• Osmophobia
• Dizziness
• Tension Headache
• Stress induced
• More frequent, less severe
• Episodic or Chronic
• Migraine Variants
• Abdominal migraine, cyclic emesis, benign paroxysmal vertigo
• Basilar Migraine
• Complicated Migraine
• Dizziness
• Ataxia
• Tinnitus
• Hearing problems
• Bilateral paresthesias
• Weakness
• Altered consciousness
• Syncope
• Hemiplegic Migraine
• Complicated Migraine
• Unilateral weakness → looks like a stroke
• Ophthalmoplegic
• Complicated Migraine
• Transient impairment of extraocular muscles
• Reverible visual loss

• Trauma
• Vascular Disorder
• Hydrocephalus
• Intracranial or systemic infection
• Neoplasm
• Substance abuse
• Raised ICP
• Hypoxia
• Metabolic disorders

• Prophylactics
• Beta Blockers (propanolol)
• TCAs
• Ca Channel Blockers
• Depakote
• Topamax
• Cyproheptadine
• Abortive
• NSAIDs
• Ergots (DHE)
• Anti-emetics
• Triptans
• 5-HT receptor agonists
• Induce vasoconstriction
• All end in "triptan"
• Contraindicated in complex, basilar migraine, angina, HTN, and use of MAOIs

• Both vocal and motor tics for > 1 year and onset before 18 yrs of age
• Etiology: Not known but thought to involve Dopaminergic Hypersensitivity
• Comorbidities
• ADHD- 2/3 of pts
• OCD, anxiety, phobias, learning disabilities- 1/3 of patients
• Anger issues- 1/4 of patients
• Lab Evaluations
• Thyroid Screen, Toxicology screen
• Anti-steptolysin O-Possible Sydenham's chorea
• Movemet disorder after Group A Strep infection
• Cooper/ceruloplasmin-Wilson's Disease
• EEG is not helpful
• Treatment
• α2-agonists-Clonidine, Guanfacine
• Helpful with ADHD but can cause sedation
• Takes 6 weeks to start working
• 1st line treatment
• Atypical Neuroleptics-risperidone, olanzapine, ziprasidone
• Blocks 5-HT, ACh, and adrenergic receptors
• Less D2 blocking
• Can cause weight gain, sedation, fever exrapyramidal symptoms
• 2nd line treatment
• Typical Neuropletics- Haldol, Orap,
• Strong D2- receptor blockers
• High incidence of extrapyramidal symptoms (Tardive Dyskinesia)
• 3rd line treatment
• SSRI for OCD
• Stimulants (Ritalin, Adderall) and SNRIs (atomoxetine) for ADHD
• TCAs, SSRI for depression

Partial-from onset it begins from one focus/hemisphere

• Simple Partial-without alteration of consciousness
• Complex Partial- with alteration of consciousness
• Can present with or without secondary generalization
• Generalized-involves both hemispheres
• Absence
• Aka Petit Mal Epilepsy
• +/- automatisms
• Presents with staring spells
• Hyperventilation precedes seizures
• Treat with 100% O₂
• Often noticed by teachers with poor school performance ("Day Dreaming")
• Classic 3 Hz spike wave EEG
• Tonic-clonic, myoclonic

• Accounts for 6% of childhood epilepsy
• Refractory tonic, myoclonic, atypical absence, atonic seizures
• 1-2 Hz spike wave on EEG
• Poor Prognosis
• MR
• Refractory to treatment

• MR
• Hypasrrhythmia-choatic EEG pattern
• Spasms
• Can progress to LGS
• Association with tuberous sclerosis, HIE, TORCH< and stroke
• Can be idiopathic
• Poor prognosis
• Treat with ACTH, vigabatrin, topiramate

• MC epilepsy o children (15%)
• Onset 6-8 yrs
• Offset 12-16 yrs
• Rolandic area of the brain controls movement of face and part of arm
• Only Nocturnal seizures
• Normal intelligence and development
• Frequnt unilateral centro-temporal spikes during sleep

• Late childhood, early adulthood onset (puberty)
• Normal intelligence
• F>M
• Familial, AD, chromosome 6
• Triggered by photic stimulation
• Myoclonic jerks, generalized tonic-clonic seizures (GTCs), absence seizures
• Easily controlled but LIFETIME treatment
• Treat with Valproate or Lamotrigine

• Nonepileptic Seizures
• Associated with HHV-6 infection
• 1/2 risk of recurrence
• No increase in epilepsy
• Age 6 months to 6 yrs
• Seizure <15 mi
• Less than 2/day
• Generalized and with fever
• Normal development and neuro exam

Nonepileptic seizure

Increased risk of epilepsy

• Nonepileptic Seizure
• Trashing/Flailing, hip-thrusting
• Precipitated and extinguished on suggestion
• No incontinence
• Duration
• History of psych issues-sexual abuse
• 15% of epileptics also have pseudo seizures
• Continuous EEG during helps distinguish from epileptic seizure
• Treat with counseling

• To keep balance, ataxic kids will walk bent forward with feet wide apart taking irregular steps as if they are drunk
• Acute Ataxia
• Chronic Ataxia
• Dandy-Walker Malformation
• Ataxia Telangiectasia

• Post-infectious cerebellitis
• Opsoclonus myoclonus
• Multiple sclerosis (MS)
• Stoke
• Basilar  migraine
• Benign paroxysmal vertigo

• Chronic ataxia
• MC inherited AR  ataxia
• GAA trinucleotide repeat
• Develops peripheral neuropathy and loss of posterior columns
• 2/3 develop cardiomyopathy
• 10% have diabetes

• Chronic Ataxias
• Cerebellar hypoplasia leads to cystic dilaton of the 4th ventricle (ventriculomegaly)
• Dilation of posterior fossa

• Chronic ataxia
• AR progressive ataxia disorder on chromosome 11
• Early symptoms:
• Truncal ataxia
• Poor Walking
• Late symptoms:
• Tremor, hypotonia, dysarthria, MR
• Chorea very late in disease
• Oculocutaneous telangiectasias begin 3-6 yrs
• Bulbar conjunctiva, face, ears, and palate
• Immunodeficiency-high frequency of sinopulmonary infetions and increased risk of lymphoma and leukemia
• Cortical cerebella degeneration
• Demyelination of posterior columns, spinocerebellar tracts, anterior horn cells, and peripheral nerves

• Congenital heart disease
• Acquired cardiomyopathy
• Coagulation disorders
• Congenital vascular anomalies
• Sickle Cells disease
• Vasculitis

• X-linked recessive disorder in dystrophin gene
• Prominent calves with proxial weakness
• (+) Gower's sign
• Waddling gait
• Prominent lordotic posture
• CPK is 10K to 30K
• Diagnosis via biopsy and deletion genetic test
• Begins < 5 yr old, Lost Ambulation < 15 yrs old

• X-linked recessive
• Less Severe than Duchenne
• Onset > 5 yrs, ambulation lost > 15 yrs

• AD disorder due to a trinucleotide repeat
• Juvenile form associated with MR (80%) and diabetes (20%)
• Congenital form presents with newborn hypotonia (proximal > distal)
• History of reduced fetal movement and polyhydramnios
• Lack of muscle development leads to arthrogryposis (contractures)
• Features include:
• Frontal baldness
• Wasting of masseter and temporal muscles
• Cataracts
• Wasting of sternocleidomastoid
• Characteristic head shape-long narrow face

• Release of myoglobin after muscle cell breakdown
• Renal Failure
• Causes: Trauma, strenuous exercise, EtOH, drugs (statins, azathioprine), inflammatory myopathy

• Mitochondrial Disease-mother inheritance
• Degenerative disorder affecting optic nerves and ganglion cells of the retina
• More common in Males
• Onset 18-25 yrs
• Central vision loss that progressively spreads to periphery
• Can also have seizures, ataxia, spasticity, MR

• Mitochondrial Disease-Maternal inheritance
• Progressive external ophthalmoplegia, cardiac conduction defects, retinitis, pigmentosa, myopathy, dementia, and seizures
• Ragged Red Fibers on muscle biopsy
• High CSF lactate

• Mitochondrial Disease- Maternal Inheritance
• Myoclonic/Generalized epilepsy with ragged red fibers
• Dementia
• Ataxia
• Spasticity
• Sensorineural Deafness
• Cardiac involvement

• Mitochondrial Disease-Maternal inheritance
• Presents in  1st year of life with:
• Abnormal extra ocular movement
• Optic atrophy
• Cerebellar dysfxn
• Cardiomyopathy
• Peripheral neuropathy
• Labs show increased lactate
• MRI shows abnormal signal in the basal ganglia and putamen
• Cause by cytochrome c deficiency
• Very poor prognosis

• Mitochondrial myopathy, encephalopathy, lactic acidosis, stroke-like symptoms
• Mitochondrial disease-maternal inheritance
• Produces stroke-like episodes in parieto-occipital region
• Focal necrosis at cortex, white matter, thalamus, and basal ganglia
• Ragged red fibers on muscle biopsy
• Lactic Acidosis
• Seizures
• Deafness
• MR
• Metabolic Stroke: Does not follow vascular borders
• Mutation on tRNA for Leu at 3243 is common

Skin

CNS
PNS

eyes

Heart

Kidney

Bone

Lungs

GI tract

• AD dominant
• Variable penetrance
• Cutaneous Lesions
• Facial adenoma sebaceum
• Ash Leaf macules- hypopigmented regions
• Shagreen patches-rough patches of skin often present in sacral spine region
• Subungual and gingival fibromas
• Cortical tubers-pale, hard, gliotic tissue
• Subependymal noduls-calcified
• Seizures very common (75% with infantile spasms)
• MR (50%)
• Angiomyolipomas of kidneys (80-100%)
• Retinal phakomas (80%)
• Hyperostosis of bone (50%)
• Rhabdomyomas of heart (30%)
• Cystic fibromyomata of lungs (10%)

Neurofibromatosis 1

NF1

• AD disorder on chromosome 17
• MR (10%)
• Learning Disabled (40%)
• Diagnosis need 2 of 7:
• 6+ cafe-au-lait spots
• 1 plexiform or 2 non-plexiform neurofibromas
• Disfiguring masses
• Plexiform is larger and at a higher risk of malignant transformation to neurosarcoma
• Optic glioma
• Inguinal or axillary freckling
• Lisch nodule- iris hamartoma
• Bony involvement
• 1st degree relative with NF 1

• AD disorder on chromosome 22
• Presents with hearing loss, ataxia, tinnitus, visual disturbances, headache, and seizures
• Bilateral CN VIII schwannoma
• 1st degree relative and either
• Unilateral CN VIII mass
• Neurofibroma
• Meningioma
• Glioma

• Sporadic Disease
• Develop facial angioma in the trigeminal distribution of face, eyes, leptomeninges
• Port wine stain
• Leptomeningeal angiomas MC occur in ipsilateral PO lobe
• CL hemiparesis, Homonymous hemianopsia, unilateral gyral intracranial calcifications
• CNS pathology is due to abnormal proliferation of endothelial vessels
• Seizures (90%)
• MR (40-50%)
• Contralateral hemiparesis (25-50%)
• Often with hemiatrophy and sensory loss
• Glaucoma (25%)

• Microcephaly vera is based on genetic/familial factors and is the MC microcephaly
• Defective neurulation
• Anencephaly
• Encephalocele
• Defective prosencephalization
• Agenesis of corpus callosum
• Holoprosencephaly
• Defective cellular migration
• Chromosomal disorders

• Intrauterine disorders
• Infections, toxins, vascular
• Perinatla brain injury
• HIE
• Meningitis
• Encephalitis
• Stroke
• Post-natal systemic Disease
• Malnutrition
• Cardiopulmonary disease
• infections

• Aqueductal stenosis
• Infectious
• X-linked
• Chiari or Dandy Walker malformations
• Mass lesions
• Abscess
• Hematomas
• Tumor
• Vascular Malformation

• Inhibit CSF absorption
• Infection > tumor > bleeding
• Meningitis, hemorrhagic, choroid plexus papilloma, meningeal malignancy, mucopolysaccharidosis, acondroplasia

Head Control: 12 weeks

Sits with Support: 26-28 weeks

Sits Alone: 40 weeks

Crawls: 40 weeks

2-3 words: 1 year

Stands: 15 Months

Phrases: 18 months

Toliet Trained 30-36 months  

Reflexive, social smile: Birth- 3 months

Babbles: 3-12 months

Words: 11-24 months

Sentences: 18-36 months

Complex Speech: 2- 7 years

• Neuroepithelial Tissue
• Astrocytes-astrocytoma, anaplastic astrocytoma, glioblastoma multiforme (GBM), pilocystic astrocytoma
• Oligodendocytoma
• Ependymomas, myxopapillary, ependymomas
• Embryonal tumors- PNET, medulloblasoma
• Meninges
• Tumor of meningoepithelial cells- meningioma
• Typically benign
• Tumors of mesenchymal non-meningothelial tumors
• Lipoma, Hemangiopericytoma, Chondrosarcoma
• Cranial and Spinal Nerves
• Schwannoma
• Neurofibroma
• Sellar Region
• Adenohypophyseal-pituitary ademona
• Craniopharyngioma

• Sources: Lungs, breast, kidney, GI, melanoma
• Hemorrhagic Mets:
• Melanoma
• Choriocarcinoma
• Renal Cell Carcinoma
• Radiosensitive Mets
• Small Cell Lung Cancer
• Germ cell tumors (medulloblastoma)
• Lymphomas
• Leukemias
• Multiple myelomas

METS can arise anywhere!!!

• Pituitary tumor-microadenoma or macroadenoma
• Often are functional tumors producing hormone
• May present with amenorrhea
• Craniopharyngioma
• Meningioma
• Germ cell tumors-Chorio CA, teratoma, germinoma, embryonal CA
• Hypothalamic or optic chiasm glioma

Differential Diagnosis of tumors in

Cerebellopontine Angle

METS can arise anywhere

• Schwannoma, acoustic neuroma
• Grows large and patient presents with dizziness, hearing loss, headache
• Meningioma
• Epidermoid and dermoid
• Extension from other areas
• Craniopharyngioma with drape over the CPA
• Gliomas, pituitary ademonas, medulloblastomas

Differential Diagnosis of tumors in

Pineal Region

METS can arise anywhere

Germ cell tumors

Pineal parenchymal tumors

Astrocytoma

Meningiomas

Melanomas

• Biopsy
• Resection
• Decompression/debulking
• Relief of symptoms
• No intervention

• Lesion to dominant parietal lobe
• Left in most people
• Agraphia without alexia-can read but cannot write
• Left-right confusion
• Digit/Finger agnosia- inability to identify finger by name
• Acalculia-mathematical aphasia

• Masses press directly on quadrigeminal plate (pineal region tumor)
• Elevated ICP secondary to compression of mesencephalic tectum by dilated suprapineal recess (hydrocephalus)
• Upgaze palsy
• Mydriasis (dilation of pupil)
• Lid retraction
• Nystagmus retractorius (up-down)
• Dissociated near-light response
• Accommodates to near objects, no reflex to light

• Vascular

o   Migraine +/- aura

o   Complicated migraine—hemiplegic, ophthalmoplegic, basilar

o   Cluster—males > females

o   Toxic vascular

o   Hypertensive

• Tension-Type—MC headaches

o   Episodic or chronic

o   Depressive, anxiety, cervical osteoarthritis, chronic myositis

• Traction and inflammatory headache
•   Mass lesions, diseases of eye, ear, nose, throat, and teeth
•  Arteritis, phlebitis, cranial neuralgias
•  Occlusive vascular DZ
•  Atypical facial pain
• TMJ DZ

•  Acute recurrent headaches will have attacks with asymptomatic periods b/t episodes
• Singular acute headaches of worsening severity and without Hx of prior headaches are concerning for secondary causes
• Chronic, progressive headaches have chronically worsening Sx—also concerning
• Chronic, nonprogressive headaches are baseline headaches superimposed with particularly bad days

b.      Cortical Spreading Depression of Leao

                                i.      Migraine is associated with a depolarization and hyperpolarization with hypoperfusion and hyper-perfusion during attack

                        Rapid influx of Calcium

                              ii.      Responsible for neurologic Sx—visual, sensory, and speech disturbances

o   Fortification spectra (teichopsia = zigzags)—visual Sx

o   Paresthesias—2^nd MC aura

c.       Trigeminovascular Theory—Mechanism

                                i.      Trigger increases serotonergic and noradrenergic stimulation in brainstem

                              ii.      Leads to dilation of cerebral and scalp blood vessels and neuropeptide release (substance P, CGRP, neurokinin A)

                            iii.      Stimulates trigeminal nerve branches

o   Thalamus à cortex à pain

o   CTZ à nausea and vomiting

o   CTZàhypothalamusàphotophobia

                            iv.      Triptans are a 5-HT agonists used in treating migraines  (work on 1b/1d receptors of 5-HT.

o   Block neuropeptide release

§  Leads to vasoconstriction (by inhibiting 5-HT3 1b receptor) and reduced inflammation

d.      Characteristic features

                                i.      3:1 ratio of women to men

                              ii.      Peaks in 25-55 yo range

                            iii.      Temporal association with menstrual cycle

                            iv.      Paradoxical relationship to sleep

o   Frequently occur during sleep or upon awakening but also abated during sleep

                              v.      Family Hx of migraine—70%

                            vi.      Cognitive impairment (reversible)

                          vii.      Dizziness, vertigo

                        viii.      Food and drink triggers

o   Ripened cheese (pizza), chocolate, MSG (Asian food), caffeinated beverages, alcohol, skipping meals

a.       MC

                                i.      Headache lasting 4-72 hours untreated or unsuccessfully treated

                              ii.      Must have at least 5 attacks

                            iii.      Headache has at least two of the following:

o   Unilateral

o   Pulsating

o   Moderate-to-severe pain

o   Causes avoidance of routine physical activity or is aggravated by physical activity

                            iv.      Headache is associated with at least one of the following:

o   Nausea/vomiting

o   Photophobia and phonophobia

                              v.      Can’t be attributed to another disorder

            Ocular Prodromata; visual aura

a.      Excitatory                                                                                                                               Irritability, elation, hyperactivity, yawning, food craving, photophobia, increased bowel

b.      Inhibitory

            Poor concentration, mental/physical slowing, word finding, Difficulty, weakness/fatigue, chill,     anorexia, constipation, abdominal bloating.

                                i.      Neurologic Disorders

o   Stroke—esp. in women <45yo

o   Epilepsy

o   Positional vertigo

o   Essential tremor—use propanolol

                              ii.      Medical Disorders

o   Raynaud’s syndrome

o   Irritable bowel syndrome

o   Interstitial cystitis

o   Asthma—avoid propanolol

o   HTN or hypotension

o   Mitral valve prolapse

o   Angina/MI

                            iii.      Psychiatric Disorders

o   Depression, panic disorders

o   Anxiety disorders, phobias

o   Bipolar illness

a.       Acute (Abortive) Treatment of Migraine

                                i.      Triptans—#1 option

                              ii.      Antiemetics, antinauseants

o   Promethazine, metoclopramide, prochlorperazine

§  Used alone or in combination with other Tx

                            iii.      NSAIDs, combination analgesics (e.g. Excedrin Migraine)

                            iv.      Ergot alkaloids

o   Dihydroergotamine, etc.

o   GI effects

b.      Preventive Treatment of Migraine

                                i.      Group 1—Best

o   Amitriptyline, valproate, propanolol, timolol,

o   Topiramate (MC)—associated with kidney stones!

                              ii.      Groups 2-5 in descending efficacy

  iii. Classes include Beta blockers, Ca channel blockers, TCAs, Anti-convusants

1.     MC type of headache

Acute or Chronic: HA ≥ 15 days/month for > 3months

a.       Lasts hours or may be continuous

b.      At least 2: bilateral, pressing/tightening, non-pulsating, mild or moderate, not aggravated by physical activity

c.       Both of the following: no more than one photophobia, phonophobia or mild nausea, neither moderate nor severeN/V     

d.   Not attributed to another disorder

a.       Warning Signs and Symptoms

                                i.      “A” headache (that is not recurrent)

                              ii.      Sudden, explosive onset (thunderclap)

                            iii.      Onset > 50 yo

                            iv.      System Sx—fever, myalgias, weight loss

                              v.      Systemic DZ—malignancy, HIV

                            vi.      Change in headache pattern

o   Progression with loss of headache-free periods

o   Change in frequency or severity

                          vii.      Neurologic Sx or asymmetric exam

o   Cognitive changes

o   Asymmetry on expansion

o   Hemiparesis

b.      Red Flags (Increased ICP)

                                i.      “Worst headache of my life”

                              ii.      Recent onset with increasing severity and frequency

                            iii.      Awakens patient or night

                            iv.      Associated with straining

                              v.      Progressive lethargy or personality change

                            vi.      Nausea, vomiting (especially projectile)

                          vii.      Visual difficulties

                        Black spots suggest ischemia to optic nerve fibers in papilledema

                        viii.      Focal weakness

                            ix.      Ataxia

    i.      Presentation

o   “Worst headache in my life!”

o   Relatively young patient; 50% mortality

o   N/V

o   Meningismus—neck stiffness

o   Focal neurologic signs

o   Transient loss of consciousness

o   Increased BP, seizure

ii.      Common sites of intracranial aneurysm—circle of Willis

o   Berry aneurysms; often multiple

  i.      Symptoms include

o   Headache (90%)

o   Pulsatile tinnitus

o   Horner’s syndrome (miosis, ptosis, etc.)

o   Monocular blindnessàdissection up to ophthalmic artery

o   Bruit

ii.      Congenital fibromuscular dysplasia

 iii.      MC due to trauma

Temporal (Giant Cell) Arteritis

 i.      Characteristics

o   >50 yo pts; MC in females 2:1

o   Elevated ESR/WSR (~70%) and CRP

o   Positive temporal artery Bx (~40%)

§  Mononuclear cell infiltrate of intima and media

§  Skip lesions present

§  Intracranial/intracerebral arteries also affected

o   Responsive to steroids!

§  Autoimmune DZ

  ii.      Signs and Symptoms

o   Localized headache (~80%)

o   Weight loss, night sweats, fever

o   Arthralgias

o   Jaw claudication (50%)—pain with more use (chewing)

§  Ischemia chewing muscles

o   Polymyalgia rheumatica (40%)—migrating muscle pain

o   Blindness if untreated/undertreated

§  Inflammation occludes posterior choroidal artery of retina

i.      Pain secondary to traction

o   Increased pain with increased ICP

  ii.      Tumor localizes with headache only in 1/3 of cases

o   Frontal headache—mass above tentorium

o   Neck/occipital pain—mass below tentorium

o   Pain in vertex: chiasmal

 i.      Pain is produced by inflammatory rxn in nasal mucosa and sinus ostia leading to occlusion and pressure

o   Structural abnormalities, allergies, polyps, etc.

   ii.      Diagnosis with plain film, CT, MRI

  iii.      Sx: Fever, purulent nasal drainage, toxic appearance, tenderness, worse at night, in children there may be no drainage.

  iv.      If untreated/undertreated:

o   Cavernous sinus thrombosis

o   Meningitis or intracerebral abscess secondary to local extension

o   Retro-orbital abscess

o   Cranial nerve palsies—eyes!

§  CN II, III, IV

§  CN VI is most susceptible to traction due to it having the longest intracranial, extra-axial course

SNOOP

Indications of secondary headache

Systemic sx: fever, chills, weight loss, new onset in patient with malignancy, immunosuppression or HIV, Tumor, abscess, temporal arteritis or meningitis

Neurologic: Motor, sensory loss, diplopia, ataxia and abnormal neuro exam, Malignant, inflammatory, vascular disorders

Onset sudden: HA reaches peak in <1 min

                        Vascular (subarachnoid, CVA, carotid dissection etc.)

 Onset after age of 50:  Neoplastic, inflammatory, temporal arteritis                                                                          

Pattern change:

    Progressive: Malignant, Inflammatory, vascular

    Precipitated by Valsalva: Chiari, lesions (primary or mets), hydrocephalus

    Postural aggravation: low pressure HA syndrome, cervicogenic HA, IC HTN, POTS

a.       Systemic, CNS infections                               h. Vascular

b.      Toxins                                                             i. hemorrhage

c.       Postseizure                                                      j. collagen vascular dz

d.      Electrolyte imbalance                                      k. exertion

e.       Post LP (positional, low pressure)                  l. shunt malfunction

f.       Head trauma

g.      Embolism

a.       Sinusitis                                                          

b.      Otitis Media                                                   

c.       Dental disease

d.      Trauma

e.       Occipital neuralgia

f.       TMJ

a.       Vascular disease                                              e. hypoglycemia

b.      Intoxication (CO poisoning)                             f. exertion

c.       MELAS

d.      Postseizure

a.       Tumor                                                             

b.      Pseudotumor cerebri (tx with acetazolamide)        

c.       Brain abscess

d. Subdural hematoma

e. Hydrocephalus

                                i.      Abnormal neuro exam

                              ii.      Headache with worrisome Sx or signs

                        Awakening from sleep, worsening valsalva

                            iii.      New headache in older populations

                            iv.      Atypical headache features or failure to meet full criteria for migraine

                                i.      Unexplained fever—AFTER neuroimaging

                              ii.      Suspected pseudotumor cerebri

                            iii.      Suspected subarachnoid hemorrhage

                            iv.      Fever of undetermined origin in children

a.       C1-C7

b.      Facets in the axial plane-allows for front to back movement

                                i.      C1/2 are good for lateral bending

o   Atlas and axis, respectively. Atlas rotates on the Axis.

o   Atlas subject to Jefferson Fracture (stable fracture).

o   Axis subject to Odontoid Fracture (Type 1 stable, Type 2 unstable, Type 3 stable) and Hangman’s Fracture (unstable fracture).

                              ii.      C5/6 are good for forward bending

                            iii.      C7—vertebra prominens

                            iv.      45^o angle

                              v.      Eight cervical nerve roots

                            vi.      Eight cervical nerve roots—C1-C7 exit above their vertebral body; C8 below

                          vii.      Cervical Radiculopathy—nerve root compression. Painless weakness. Dermatomal pattern. Look for positive spurlings.

                        viii.      Cervical Myelopathy—spinal cord compression. Long tract

signs. Look for Lhermittes, Hoffman’s, clonus, + Babinski.

                            ix.      Cervical spinal stenosis

o   Presents with myelopathy (hands tingling, etc.)

• Facets in the coronal plane-allows for more rigid structure, rib          expansion
•  Twelve vertebrae and nerve roots: exit below their vertebral bodies.
• 60^o angle

 i.      Facets in the sagittal plane-allows for rotation. Weight-bearing.

  ii.      Five nerve roots—exit below their vertebral bodies.

  iii.      Lumbar Radiculopathy—nerve root compression. Painless weakness. Dermatomal pattern. + SLR lower roots. + Reverse SLR upper roots.

  iv.      Lumbar Myelopathy—spinal cord compression. Long tract signs. Cannot occur below the level of conus medullaris. Clonus, + BabinskiFive vertebrae and nerve roots

o   90^o angle

  v.      Spinal cord ends at L1/2 level

 vi.      Lumbar spinal stenosis

o   Presents with radiculopathy and neurogenic claudication

 i.      C6/7 > T2/T3

 ii.      Intervertebral disks composed of nucleus pulposis (center; type III collagen, shock absorber) and annulus fibrosis (rim; type II collagen).

iii.      Disk bulge: nucleus pulposis bulges but is still contained.

 iv.      Disk herniation: nucleus pulposis leaks out of the annulus fibrosis.

 v.      Ligaments work together to maintain normal alignment and decrease shear force on the spine.

vi.      The spinal cord ends at L1 or L2. If it ends below this, the patient may have a tethered cord.

 vii.      The spinal canal ends at S2

 viii.      Masqueraders of Spinal Disease: Intrinsic shoulder pathology, Intrinsic hip pathology, ALS, Parsonage-Turner syndrome.

a.     Motor

                                i.      From motor cortex in precentral gyrus down through internal capsule to cerebral peduncles

                              ii.      Decussates in lower medulla in medullary pyramids

                            iii.      Innervate contralateral side of body

Dorsal Column (Medial Lemniscus) Pathway

 i.      Rises in dorsal columns as it becomes the medial lemniscus in the brainstem

  ii.      Decussates in lower medulla lemnisci

iii.      Synapse in VPL, end in somatosensory cortex of postcentral gyrus

iv. Sensory and concious propreception

 i.      Pain and temperature sensation

 ii.      Decussates immediately at level of entry in spinal cord

 iii.      Rises through reticular formation, synapses in VPL, and ends in somatosensory cortex

i.      LMN lesion specific to a muscle

o   Typically not painful unless there is a compression/entrapment

o   Rarely manifests with myelopathy

a.  Nerve root lesion

                                i.      LMN at nerve root level

o   Presents with pain in specific, affected groups

                              ii.      Decreased reflexes, atrophy

a.       Myelopathy—spinal cord myelopathy

                                i.      UMN lesions

                              ii.      Present with spasticity, clonus, hyperreflexia, + Babinski

o   No atrophy