Vogt-Koyanagi-Harada (VKH) syndrome

Vogt-Koyanagi-Harada (VKH) syndrome is a rare systemic disease involving various melanocyte-containing organs. Bilateral panuveitis associated with cutaneous, neurologic, and auditory abnormalities are manifestations of this inflammatory granulomatous disorder. VKH syndrome was first noted in the 10th century by a Persian ophthalmologist, Ali Ibn Isa, who described a case of poliosis associated with ocular inflammation. This association was reported again in 1873 by Schenkl, in 1892 by Hutchinson, and in 1906 by Vogt. In 1926, Haradadescribed a patient with idiopathic uveitis affecting the posterior segment, with retinal detachment and meningeal irritation. Koyanagi reported similar cases in 1929. Babel, in 1932, suggested that symptoms of the disorder described by Vogt, Koyanagi, and Harada were manifestations of the same single entity, referred to as Vogt-Koyanagi-Harada syndrome or uveoencephalitis.

Pathophysiology

The etiologic and pathogenic factors in VKH syndrome remain unclear. The clinical course of VKH syndrome with an influenzalike episode suggests a viral or postinfectious origin. Some studies invoke a possible role of Epstein-Barr virus reactivation in this disease.Although a viral cause has been proposed, no virus has been isolated or cultured from patients with VKH syndrome. Morris and Schlaegel found viruslike inclusion bodies in the subretinal fluid of a patient with VKH syndrome.
Clinical and experimental data continue to support an immunologic etiology. An autoimmune reaction seems to be directed against an antigenic component shared by uveal, dermal, and meningeal melanocytes. The exact target antigen has not been identified, but possible candidates include tyrosinase- or tyrosinase-related proteins, an unidentified 75-kd protein obtained from cultured human melanoma cells (G-361), and S-100 protein. Evidence suggests that Th1 and Th17 subsets of T cells together with cytokines interleukin (IL)–23 and IL-17 are likely involved in the initiation and maintenence of the inflammatory process.
VKH syndrome can be associated with other autoimmune disorders such as autoimmune polyglandular syndrome,hypothyroidism, Hashimoto thyroiditis, diabetes mellitus,Guillain-Barré syndrome, and IgA nephropathy.
Single reports of patients developing VKH syndrome after cutaneous injury have been noted, as well as 2 cases of this condition occurring after BCG therapy for melanoma and 1 case following surgery of metastatic malignant melanoma. Case reports indicate that even an indirect trauma in melanocyte-containing tissue may induce an inflammatory response within the eye, with Vogt-Koyanagi-Harada disease following a closed head trauma. Cases of this syndrome were reported to be linked to malignant lymphoma.
Immunologic analysis of cerebrospinal fluid (CSF) lymphocytes in VKH syndrome and studies of human uveal melanocytes show that uveal pigment can stimulate lymphocyte cultures from patients with VKH syndrome. Lymphocytes of peripheral blood and CSF from these patients may reveal in vitro cytotoxicity against allogenic melanoma cells.
Circulating antibodies against a retinal photoreceptor region have been detected in patients with this disorder.
The possibility that VKH syndrome has an autoimmune pathogenesis is supported by the statistically significant frequency of HLA-DR4, an antigen commonly associated with other autoimmune diseases. VKH syndrome has been closely associated with HLA-B54, HLA-DR4, and HLA-DR53 in Japanese patients ; with HLA-DR4, HLA-DRw53, and HLA-DQw3 in subjects of Native American ancestry; with HLA-DR1 and HLA-DR4 in Hispanic patients living in southern California; and with HLA-DR4 and HLA-DQw7 in Chinese patients.  HLA-DR4 also was found to be significantly related to VKH syndrome in white Europeans, specifically in Italian patients. These findings confirm the possibility of immunogenic predisposition and the decisive role of HLA-DR4 antigen in the development of the disease.
Data indicate that patients with VKH syndrome are sensitized to melanocyte epitopes and display a peptide-specific Th1 cytokine response. Patients bearing HLA-DRB1*0405 recognize a broader melanocyte-derived peptide repertoire, so the presence of this allele increases susceptibility to the development of VKH disease. In a group of French VKH syndrome DRB1*04-positive patients, the HLA-DRB1*0405 subtype was found in 71%^.
A recent study revealed that a decreased vitamin D-3 level has been associated with active intraocular inflammation in VKH syndrome patients.

Epidemiology

Frequency

United States

VKH syndrome is rare. No precise data are available regarding frequency of the disease.

International

VKH syndrome is rare but widely distributed.

Mortality/Morbidity

VKH syndrome is not associated with mortality. Acute disturbances in hearing and vision may occur, and the cutaneous changes may be permanent.

Race

VKH syndrome occurs more frequently in individuals with darker pigmentation (eg, persons of Asian, Native American, Latin American, or black heritage). VKH syndrome is one of the most common forms of uveitis among pigmented races. The manifestations of VKH syndrome in whites resemble those in the Japanese population. However, cutaneous signs are much more rarer.

Sex

Women appear to be affected with VKH syndrome more frequently than men.

Age

The onset of VKH syndrome has been reported to range from 3-89 years, with a maximum frequency in the thirties. Although often unrecognized, VKH syndrome may affect children.

History

VKH syndrome is usually preceded by a prodromal stage of nonspecific symptoms including headache, increased sensitivity to touch of the hair and skin, vertigo, nausea, nuchal rigidity, vomiting, and low-grade fever that may last a few days. Patients usually initially present to an ophthalmologist for ocular problems, including sudden loss of vision, ocular pain, and photophobia. Hearing disturbances and dizziness may be present. After weeks or months, most patients notice cutaneous signs (eg, hair loss, poliosis, vitiligo).

Physical

The American Uveitis Society developed the first diagnostic criteria for VKH Syndrome in 1978. In addition to an absence of prior ocular trauma or surgery, at least 3 of the following 4 criteria should be met to confirm the diagnosis of VKH syndrome:

• Bilateral chronic iridocyclitis
• Posterior uveitis, which may include exudative retinal detachment, optic nerve swelling, or atrophy of the retinal pigment epithelium
• Cerebrospinal fluid pleocytosis or evidence of tinnitus, dysacusis, headache or meningismus, or cranial nerve involvement
• Cutaneous findings of vitiligo, alopecia, or poliosis

Revised diagnostic criteria were established by International Committee of Experts during The First International Workshop on VKH Disease in 1999.^[33] The new criteria allowed for diagnosing VKH Syndrome in different stages of the disease, specifically addressing the early stages during which cutaneous findings are often not present.

Criteria for VKH syndrome (1-5)

1. No history of penetrating ocular trauma or surgery preceding the initial onset of uveitis
2. No clinical or laboratory evidence suggestive of other ocular disease entities
3. Bilateral ocular involvement - (a) or (b) must be met, depending on the stage of disease when the patient is examined, based on early and late manifestations below.
Early manifestations of the disease
(1) There must be evidence of a diffuse choroiditis (with or without anterior uveitis, vitreous inflammatory reaction, or optic disk hyperemia), which may manifest as one of the following: (a) focal areas of subretinal fluid or (b) bullous serous retinal detachments.
(2) With equivocal fundus findings, both of the following must be present as well: (a) focal areas of delay in choroidal perfusion, multifocal areas of pinpoint leakage, large placoid areas of hyperfluorescence, pooling within subretinal fluid, and optic nerve staining (listed in order of sequential appearance) by fluorescein angiography and and (b) diffuse choroidal thickening, without evidence of posterior scleritis by ultrasonography.
Late manifestations of the disease
(1) History suggestive of the prior presence of findings from (3)(a) and either both (2) and (3) below or multiple signs from (3)
(2) Ocular depigmentation: Either (a) sunset glow fundus or (b) Sugiura sign is sufficient.
(3) Other ocular signs may include (a) nummular chorioretinal depigmented scars, (b) retinal pigment epithelium clumping and/or migration, or (c) recurrent or chronic anterior uveitis.
4. Neurological/auditory findings (may have resolved by time of examination) - Meningismus (malaise, fever, headache, nausea, abdominal pain, stiffness of the neck and back, or a combination of these factors; headache alone is not sufficient to meet the definition of meningismus) or Tinnitus, or CSF pleocytosis
5. Integumentary findings (not preceding the onset of CNS or ocular disease) - Alopecia, or Poliosis, or Vitiligo
Complete VKH disease is if criteria 1-5 are present.
Incomplete VKH disease is if criteria 1-3 and either 4 or 5 are present.
Probable VKH disease is isolated ocular disease; criteria 1-3 must be present.
The classic course of VKH syndrome consists of the following 3 phases:

1. In the meningoencephalitis phase, the degree of neurologic symptoms may vary. Generalized muscle weakness, hemiparesis, hemiplegia, dysarthria, and aphasia have been reported. Most of the neurologic symptoms have been directly attributed to changes in CSF (eg, pleocytosis, increased pressure, protein levels), inflammatory arachnoiditis, or resulting subarachnoidal adhesions. Mental changes ranging from mild confusion to psychosis may occur.
2. The ophthalmic-auditory phase is characterized by common features such as decreased visual acuity, eye pain, eye irritation, and loss of vision. Dysacusis (usually bilateral) and tinnitus develop in 50% of patients.
3. The convalescent phase is characterized by cutaneous signs developing after uveitis begins to subside, usually within 3 months from the onset of disease. Although cutaneous signs typically occur several weeks to months after the onset of ocular inflammation, skin changes have sometimes been observed many years before uveitis appeared. Pigmentary changes tend to be permanent. Poliosis, which occurs in 90% of patients, involves the eyebrows and eyelashes and, occasionally, the scalp and body hair. Poliosis affects 50% of patients and usually appears after the onset of alopecia, which may be patchy or diffuse. Vitiligo manifests in 63% of patients and is often symmetric. Most patients have perilimbal vitiligo (Sugiura sign). Atypical variants of vitiligo with inflammatory raised borders and plaque-type inflammatory erythema have also been reported. Halo nevi may be present.

Causes

The cause of VKH syndrome is unknown, but a viral factor has been suggested in the pathogenesis. An autoimmune reaction to melanocytes with the involvement of T-cell–mediated cytotoxicity and apoptosis is postulated. Although almost all instances of VKH syndrome are sporadic, and familial cases are rare, some authors suggest that the condition may be inherited, probably as an autosomal recessive trait. Numerous data demonstrate the association of HLA-DR4 antigen and VKH syndrome in different racial groups. According to some studies, the major factor contributing to susceptibility for the disease is presence of the DRB*0405 allele.

Differentials

• Alezzandrini Syndrome
• Alopecia Areata
• Piebaldism
• Vitiligo

Laboratory Studies

• For quick diagnosis and early treatment, Vogt-Koyanagi-Harada (VKH) syndrome requires a multidisciplinary management strategy involving dermatologists and ophthalmologists.
• Perform neurologic examination with lumbar puncture to detect associated abnormalities.
• Detailed CSF cell analysis is necessary. Changes in the CSF include pleocytosis with the presence of melanin-laden macrophages (specific for the syndrome and helpful in confirming the diagnosis), increased protein levels, and increased pressure.

Imaging Studies

• Standardized A-scan and contact B-scan echography, performed by ophthalmologist
• Orbital MRI
• Brain MRI

Procedures

• Perform fluorescein angiography, which shows multiple hypofluorescent areas in the retina at the level of the retinal pigment epithelium.
• Perform indocyanine green choroidal angiography.
• Audiometry may reveal sensorineural hearing loss.

Histologic Findings

A skin biopsy specimen taken a month after the onset of VKH syndrome ocular symptoms will likely reveal a mononuclear infiltrate concentrated in the area of hair follicles and sweat glands, consisting mostly of T lymphocytes with a small number of B cells. In depigmented skin, the absence of melanin, as anticipated in vitiligo, can be noted. Vasodilatation in the dermis, pigment-laden macrophages, and a lymphocytic infiltrate have also been described.

Medical Care

• For pigmentary changes with Vogt-Koyanagi-Harada (VKH) syndrome, treatment options mirror those for vitiligo.
• For eye inflammatory changes, treatment includes systemic corticosteroids, with an average initial dose of 80-100 mg of oral prednisone per day. Early, aggressive use of systemic corticosteroids and a gradual tapering of drug dosage for 6 months after presentation are recommended to prevent progression and development of complications. Some authors recommend pulse corticosteroid therapy.
• In patients whose conditions fail to respond to high-dose corticosteroid (oral or intravenous) therapy or who develop significant adverse effects, immunosuppression with cyclosporine or other antimetabolites (eg, azathioprine, cyclophosphamide, methotrexate [MTX]) may be required.
• Case reports suggest that intravenous immunoglobulins (IVIGs) and infliximab may be of interest in the treatment for VKH syndrome. Further trials are needed to assess the efficacy of these agents.
• Topical and periocular corticosteroids are used. If systemic medications are not effective,subtenon injections may be considered before intraocular treatment modalities.
• Cycloplegic-mydriatic eye drops are used symptomatically.

Surgical Care

• Surgical therapy for glaucoma is necessary in some patients. Surgical intervention includes laser iridotomy, surgical iridectomy, and trabeculectomy. 
   
   

  Consultations

  Ophthalmologists and neurologists must be consulted.
  
  
  

  Medication Summary

  The goals of pharmacotherapy are to reduce morbidity and to prevent complications.
  
  

  Corticosteroids

  Class Summary

  Have anti-inflammatory properties and cause profound and varied metabolic effects. Modify the body's immune response to diverse stimuli.
  
  

  Prednisone (Deltasone, Orasone)

   

  Synthetic adrenocortical steroid with predominantly glucocorticoid properties. Immunosuppressant for treatment of autoimmune disorders; may decrease inflammation by reversing increased capillary permeability and suppressing PMN activity. Stabilizes lysosomal membranes and suppresses lymphocytes and antibody production.
  
  
  
  

  Immunosuppressive agents

  Class Summary

  Have antiproliferative and immunosuppressive effects.
  
  
  

  Pediatric Dosing & Uses

  Dosing Forms & Strengths

  tablet

  • 50mg

  powder for injection

  • 100mg/vial

  oral suspension

  • 50mg/mL

  Safety and efficacy not established; however used as adults (off label)
  
  
  

  Pregnancy & Lactation

  Pregnancy Category: D
  Lactation: excreted at low levels in breast milk/not recommended
  
  
  

  Pharmacology

  Absorption: good (PO)
  Half-Life: 5 hr
  Duration: variable
  Plasma Concentration: <1 mcg/mL
  Protein Bound: 30%
  Metabolism: liver
  Metabolites: mercaptopurine, 6-thiouric acid
  Dialyzable: partially
  

  Pharmacogenomics

  Azathioprine is a prodrug and extensively metabolized to the active metabolite 6-mercaptopurine
  6-mercaptopurine is activated further by guanine phosphoribosyltransferase (HGPRT) to form thioinosine monophosphate (TIMP) and by kinase enzymatic pathways to form active 6-thioguanine nucleotides
  Thiopurine S-methyltransferase (TPMT) inactivates 6-mercaptopurine
  Although complete TPMT deficiency is rare in the general population (0.3%), TPMT screening should be performed prior to administration in all patients prescribed azathioprine or 6-mercaptopurine
  With TPMT deficiency, a larger proportion of 6-mercaptopurine is converted to the cytotoxic 6-thioguanine nucleotide analogues, which can lead to bone marrow toxicity and myelosuppression
  Alleles associated with decreased TPMT enzymatic activity are TPMT*2, TPMT*3A, and TPMT*3C
  
  
  

  IV & IM Information

  IV Incompatibilities

  Stable in neutral or acid solutions, but in alkaline solns is hydrolyzed to mercaptopurine
  

  IV Administration

  Can be administered IVP over 5 min at a concentration not exceeding 10 mg/mL
  Can be further diluted with NS or D5W & administered by intermittent infusion over 30-60 min (usual) but infusions ranging from 5 min to 8 hr have been done
  

  Storage

  Store powder at room temp protected from light
  Reconstituted soln is stable for 2 wk at room temp (25°C); may be less stable under refrigeration
  Use within 24 hr since no preservatives
  

  
  
  
  
  
  

   

Sarcoidosis

Sarcoidosis is a disease in which inflammation occurs in the lymph nodes, lungs, liver, eyes, skin, or other tissues.


Causes, incidence, and risk factors



The cause of the disease is unknown. In sarcoidosis, tiny clumps of abnormal tissue (granulomas) form in certain organs of the body. Granulomas are clusters of immune cells.



The disease can affect almost any organ of the body, but it most commonly affects the lungs.



Possible causes of sarcoidosis include:



*



Extreme immune response to infection

*



High sensitivity to environmental factors

*



Genetic factors



The condition is more common in African Americans than Caucasians, especially in Caucasians of Scandinavian heritage. Females are usually affected more often than males.



The disease typically begins between ages 20 and 40. Sarcoidosis is very rare in young children.



A person with a close blood relative who has sarcoidosis is nearly five times as likely to develop the condition.

Symptoms



There may be no symptoms. When symptoms occur, they can involve almost any body part or organ system in your body.



Almost all patients have lung or chest symptoms:



*



Chest pain (most often behind your breast bone)

*



Dry cough

*



Shortness of breath



Symptoms of general discomfort or uneasiness often occur:



*



Fatigue (one of the most common symptoms in children)

*



Fever

*



Joint achiness or pain (arthralgia)

*



Overall feeling of discomfort, illness, or lack of well-being

*



Weight loss (one of the most common symptoms in children)



Skin symptoms:



*



Hair loss

*



Raised, red, firm skin sores (erythema nodosum), almost always on the front part of the lower legs

*



Rash

*



Scars that become raised or inflamed



Nervous system symptoms may include:



*



Headache

*



Seizures

*



Weakness on one side of the face



Eye symptoms include:



*



Burning

*



Discharge from the eye

*



Dry eyes

*



Itching

*



Pain

*



Vision loss



Other symptoms of this disease:



*



Dry mouth

*



Fainting spells if the heart is involved

*



Nosebleed

*



Swelling in the upper part of the abdomen



Signs and tests



A physical exam may show the following:



*



Abnormal breath sounds (such as rales)

*



Enlarged liver

*



Enlarged lymph glands

*



Enlarged spleen

*



Rash



Often the disease is found in patients with visible physical signs who have an abnormal chest x-ray.



Different imaging tests may help diagnose sarcoidosis:



*



Chest x-ray to see if the lungs are involved or lymph nodes are enlarged

*



CT scan of the chest

*



Lung gallium scan



To diagnose this condition, a biopsy is needed. Biopsy of the lung using bronchoscopy is usually done. Biopsies of other body tissues may also be done.



This disease may affect the results of the following lab tests:



*



Calcium levels (urine, ionized, serum)

*



CBC

*



Immunoelectrophoresis - serum

*



Liver function tests

*



Quantitative immunoglobulins (nephelometry)

*



Serum phosphorus



Treatment



Sarcoidosis symptoms will often get better on their own slowly without treatment.



Patients whose eyes, heart, nervous system, or lungs are involved may need to be treated with corticosteroids (prednisone or methylprednisolone). Therapy may continue for 1 or 2 years. The most severely affected patients may need lifelong therapy.



Drugs that suppress the immune system (immunosuppressive medicines) are sometimes also needed:



*



The drug used most often is methotrexate, but azathioprine and cyclophosphamide are also sometimes recommended.

*



Hydroxychloroquine is useful for skin sarcoidosis.



Rarely, some people with end-stage heart or lung damage may need an organ transplant.

Expectations (prognosis)



Many people with sarcoidosis are not seriously ill, and the disease may get better without treatment. About 30 - 50% of cases get better without treatment in 3 years. About 20% of people whose lungs are involved will develop lung damage.



The overall death rate from sarcoidosis is less than 5%. Causes of death include:



*



Bleeding from the lung tissue

*



Heart damage, leading to heart failure and abnormal heart rhythms

*



Lung scarring (pulmonary fibrosis)



Complications



*



Fungal lung infections (aspergilloma)

*



Glaucoma and blindness from uveitis (rare)

*



Kidney stones from high calcium levels in blood or urine

*



Osteoporosis and other complications of taking corticosteroids for long periods of time.

*



Pulmonary hypertension
 

Narcolepsy

Narcolepsy is a sleep disorder that causes excessive sleepiness and frequent daytime sleep attacks.
Causes, incidence, and risk factors

Narcolepsy is a nervous system disorder. The exact cause is known.

In some patients, narcolepsy is linked to reduced amounts of a protein called hypocretin, which is made in the brain. What causes the brain to produce less of this protein is unclear.

There is a possibility that narcolepsy is an autoimmune disorder. An autoimmune disorder is when the body's immune system mistakenly attacks healthy tissue.

Narcolepsy tends to run in families. Certain genes are linked to narcolepsy.
Symptoms

Narcolepsy systems usually first occur during ages 15 to 30.

The most common symptoms are:

Periods of extreme drowsiness during the day. You may feel a strong urge to sleep, often followed by a short nap (sleep attack).

These periods last for about 15 minutes each, although they can be longer.

They may happen after eating, while driving, talking to someone, or during other situations.

Most often, you wake up feeling refreshed.

Dream-like hallucinations between sleep and wakefulness. They involve seeing or hearing, and possibly other senses.

Sleep paralysis. This is when you cannot move as you start falling asleep or when you first wake up. It may last up to 15 minutes.

Cataplexy. This is a sudden loss of muscle tone while awake that makes you unable to move. Strong emotions, such as laughter or anger, can trigger this.

Most attacks last for less than 30 seconds and can be missed.

Your head will suddenly fall forward, your jaw will become slack, and your knees will buckle.

In severe cases, a person may fall and stay paralyzed for as long as several minutes.

Signs and tests

The doctor will perform a physical exam and order blood work to rule out conditions that can cause similar symptoms. Conditions that can cause excessive sleepiness include:

Insomnia and other sleep disorders

Restless leg syndrome

Seizures

Sleep apnea

Other medical, psychiatric, or nervous system diseases

Other tests may include:

ECG (measures the heart's electrical activity)

EEG (measures the brain's electrical activity)

Genetic testing to look for narcolepsy gene

Sleep study (polysomnogram)

Multiple Sleep Latency Test (MSLT) to see how long it takes you to fall asleep during a daytime nap. Patients with narcolepsy fall asleep much faster than people without the condition.

Treatment

There is no known cure for narcolepsy. The goal of treatment is to control symptoms.

Lifestyle changes and emotional counseling may help you do better in work and social activities. This involves:

Eating light or vegetarian meals during the day and avoiding heavy meals before important activities

Planning naps to control daytime sleep and reduce the number of unplanned, sudden sleep attacks

Scheduling a brief nap (10 to 15 minutes) after meals, if possible

Telling teachers and supervisors about the condition so you are not punished for being "lazy" at school or work

You may need to take prescription medications to help you stay awake. The stimulant drug armodafinil is usually tried first. It is much less likely to be abused than other stimulants. Other stimulants include dextroamphetamine (Dexedrine, DextroStat) and methylphenidate (Ritalin).

Antidepressant medications can help reduce episodes of cataplexy, sleep paralysis, and hallucinations. Antidepressants include:

Selective norepinephrine reuptake inhibitors (SNRIs) such as venlafaxine

Selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine, paroxetine, or citalopram

Tricyclic antidepressants such as protriptyline or imipramine

Sodium oxybate (Xyrem) is prescribed to some patients for use at night.

If you have narcolepsy, you may have driving restrictions. Restrictions vary from state to state.
Expectations (prognosis)

Narcolepsy is lifelong (chronic) condition.

It is not deadly, but it may be dangerous if episodes occur during driving, operating machinery, or similar activities.

Narcolepsy can usually be controlled with treatment. Treating other underlying sleep disorders can improve symptoms of narcolepsy.
Complications

Difficulty functioning at work

Difficulty with social activities

Injuries and accidents, if attacks occur during activities

Side effects of medications used to treat the disorder

Calling your health care provider

Call your health care provider if:

You have symptoms of narcolepsy

Narcolepsy does not respond to treatment, or you develop other symptoms

Prevention

There is no known way to prevent narcolepsy. Treatment may reduce the number of attacks. Avoid situations that aggravate the condition if you are prone to attacks of narcolepsy.

Mnemonics for EYE

I.                   Bones of the Orbit

Roof: “Front-less”

            à frontal, lesser wing of sphenoid bone

Lateral Wall: “Great-Z”

                        à greater wing of sphenoid, zygomatic bone

            Medial Wall: “Smel(l)”

                        à sphenoid, maxillary, ethmoid, lacrimal bones

            Floor: “Zip My Pants”

                        à zygomatic, maxillary, palatine bones

II.                Eye Innervation

CN III - superior division = LPS, SR; inferior division = MR, IR, IO

CN IV – SO

CN VI – LR     

III.             Nerves in Relation to CTR (common tendinous ring)

• Nerves outside CTR: “Little Fairy Tots”

L = lacrimal    (V1)

F = frontal       (V1)

T = trochlear   (CN VI)

• Nerves within CTR: “Sits Naked In Anticipation”

S = sup. division of CN III

N = nasociliary    (V1)

I = inf. division of CN III

A = abducent     (CN VI)

[NOTE: optic nerve (CN II) runs with ophthalmic artery thru optic canal]

Head & Neck Mnemonics

Head Mnemonics

NERVES

¨ Cranial Nerves

I-optic, II-olfactory, III-oculomotor, IV-trochlear, V-trigeminal, VI-abducens, VII-facial, VIII-acoustic (vestibulocochlear), IX-glossophrayngeal, X-vagus, XI-spinal accessory, XII-hypoglossal

On Old Olympus Towering Tops, A Finn And German Viewed Some Hops

 You have I nose. You have II eyes. (I – Olfactory; II – Optic)

Motor and Sensory nerves

Some Say Marry Money, But My Brother Says Big Bras Matter More

¨ Innervation of Extraocularmotor Muscles

LR6 (SO4) 3

LR6--Lateral rectus--> VI abductens

SO4--Superior Oblique--> IV Trochlear

3--The remaining 4 eyeball movers = III

¨ Branches of Facial Nerve after Stylomastoid foramen

From superior to inferior:
Ten Zebras Bought My Car

To Zanzibar By Motor Car

Temporal, Zygomatic, Buccal, Masseteric, Cervical

PAssing Through Zanzibar By Motor Car (PA for Posterior Auricular).
Ten Zulus Buggered My Cat (PAinfully)
Temporal branch
Zygomatic branch
Buccal branch
Mandibular branch
Cervical branch
(Posterior auricular nerve)

¨ Cervical Spinal Nerves

C3-4-5 keeps the phrenic alive (innervation of phrenic nerve)

C3-4-5 keep the diaphragm alive (innervation of diaphragm)

C5-6-7 raise your arms to heaven (nerve roots of long thoracic nerve innervate serratus anterior)

¨ V3 innervated muscles

My A$$ Meets The Toilet

Mylohyoid                 Anterior digastric       Muscles of Mastication
Tensor veli palatini     Tensor tympani

¨V3: sensory branches

"Buccaneers Are Inferior Linguists"
Buccal                        Auriculotemporal      
Inferior alveolar                     Lingual

¨ Lacrimal nerve course

Lacrimal's story of 8 L's
Lacrimal nerve runs on Lateral wall of orbit above Lateral rectus, then Lets communicating branch join in, then supplies Lacrimal gland, then Leaves it and supplies Lateral upper eye Lid!

¨ CN VII innervated muscles (branchial arch 2 derivatives)

"Imagine someone making the facial expression to say 'PSS...'
Facial expression muscles:
Posterior belly of digastric
Stapedius
Stylohyoid

¨ Scalp: nerve supply

GLASS
Greater occipital/ Greater auricular
Lesser occipital
Auriculotemporal
Supratrochlear
Supraorbital

Bones/Spaces

¨ Cranial bones PEST OF 6 Parietal            Ethmoid          Sphenoid        Temporal         Occipital         Frontal The 6 just reminds that there's 6 of them to remember. Old Pygmies From Thailand Eat Skulls Old People From Texas Eat Spiders Occipital         Parietal            Frontal                        Temporal         Ethmoid          Sphenoid Prostitutes Offer Free Sex To Everyone Parietal            Occipital         Frontal                        Sphenoid        Temporal         Ethmoid          ¨ Orbit: bones of medial wall My Little Eye Sits in the orbit Maxilla (frontal process) Lacrimal Ethmoid Sphenoid (body) ¨ Foramen spinosum  location on base of skull Foramen spinosum is adjacent to the spine of sphenoid. ¨ Cavernous sinus contents O TOM CAT O TOM are lateral wall components, in order from superior to inferior. CA are the components within the sinus, from medial to lateral. CA ends at the level of T from O TOM. · See diagram.  Occulomotor nerve (III) Trochlear nerve (IV) Ophthalmic nerve (V1) Maxillary nerve (V2) Carotid artery Abducent nerve (VI) T: When written, connects to the T of OTOM. ¨ Cartilage derivatives of 1st pharyngeal arch (mandibular) I'M A Super Sexy Guy       (or Girl) Incus Malleus Anterior ligament of malleus Spine of sphenoid Sphenomandibular ligament Genial tubercle of mandible Muscles ¨ Face muscles groups cranial innervation Mandibular nerve: Mastication. Facial nerve: Facial expression. ¨ Pterygoid muscles Function of lateral vs. medial "Look at how your jaw ends up when saying first syllable of 'Lateral' or 'Medial' ": "La": your jaw is now open, so Lateral pterygoid opens mouth. "Me": your jaw is still closed, so Medial pterygoid closes the mandible. ¨ Eye rotation by oblique muscles I Love S&M Inferior oblique: Lateral eye rotation Superior oblique: Medial eye rotation Extrinsic muscles of tongue [for pro soccer fans] "Paris St. Germain's Hour": Palatoglossus Styloglossus Genioglossus Hyoglossus · PSG is a French soccer team (foreign), hence extrinsic comes to mind. Vessels Maxillary artery branches "DAM I AM Piss Drunk But Stupid Drunk I Prefer, Must Phone Alcoholics Anonymous": Deep auricular Anterior tympanic Middle meningeal Inferior alveolar Accessory meningeal Masseteric Pterygoid Deep temporal Buccal Sphenopalatine Descending palatine Infraorbital Posterior superior alveolar Middle superior alveolar Pharyngeal Anterior superior alveolar Artery of the pterygoid canal Neck Mnemonics Vessels ¨ Subclavian artery branches Very Tired Individuals Sip Strong Coffee Served Daily Vertebral artery Thyrocervical trunk ---Inferior thyroid ---Superficial cervical ---Suprascapular Costocervical ---Superior intercostal ---Deep cervical ¨ External carotid artery branches Some Aggressive Lovers Find Odd Positions More Stimulating Superior thyroid Ascending pharyngeal Lingual Facial Occiptal Posterior auricular Maxillary Superficial temporal Sister Lucy's Powdered Face Often Attracts Silly Medicos So Long For Acting Old Parenting Means Stability Sally Ate Lots Of Fresh Produce March Through September   Nerves ¨ Cervical plexus arrangement of the important nerves "GLAST" 4 compass points: clockwise from north on the right side of neck: Great auricular (North)  à  Lesser occipital  (East) à Accessory nerve (pops out between L and S) à Supraclavicular (South) à Transverse cervical (West) Other ¨ Thoracic Duct Location The duck is between two gooses (duck = thoracic duct) 2 gooses = azyGOUS and esophaGOUS ¨ Carotid sheath contents               "I See 10 CC's in the IV": I See (I.C.) = Internal Carotid artery 10 = CN 10 (Vagus nerve) CC = Common Carotid artery IV = Internal Jugular Vein Muscles Hyoid bone: muscle attachments Christ, He Didn't Screw Girls Much. That's Obvious, Stupid The first sentence is for 6 muscles attaching superiorly, the second sentence is for 3 muscles attaching inferiorly.   Both sentences are in order from lateral to medial: Constricter (middle) Hyoglossus Digastric Stylohyoid Geniohyoid Myloyoid Thyrohyoid Omohyoid Sternohyoid

Mnemonics on basic physiology

Alimentary and Digestion

Ape Oil

The 5 sphincters found in the Alimentary Canal spell APE OIL: Anal, Pyloric, Lower Esophageal, Oddi, and Ileocecum. Also, try An Odd Pile Lowers the Ileocecum.

Cars, Piles, and the Bay of Fundy

"The CAR is FUN `til the BODY PILES" I remember the 5 layers of the GI stomach: Cardiac, Fundus, Body, and Pylorus. The fundus looks like the Bay of Fundy (to me, anyway), and the pylorus is where the food piles waiting for the sphincter to open.

Some are Ugly

The 4 lobes of the liver -- quadrate, left & right, caudate -- bring to mind the newspaper headline of the wheelchair-bound fellow who left a party right after his ugly girlfriend departed: QUAD LEFT RIGHT after Cow Date.

Dow Jones and the Cannibal

We are supposed to remember the lengths of the first 3 parts of the digestive system after the stomach, so I came up with the story of a cannibal who consumes a dozen people, including an ailing stock market analyst. It goes: One Ate 12, including an Ill Dow Jones referring of course to 1, 8, 12-feet lengths for the Ileum, Duodenum, Jejunum.
A really good device for recalling the bowels is to remember the market news: Dow Jones Industrial Averages Closing Stock Report whose initial letters also identify the Duodenum, Jejunum, Ileum, Appendix, Colon, Sigmoid, and Rectum. It misses the cecum but is otherwise unforgettable.

Quick Peritoneum Facts

The idea is to relate key letters of related parts. E.g., stomach and omentum (which lays over the stomach) share the letters OM.

• The bacterium E. coli is found in Everybody's Colon
• The Omentum covers the stomach
• The Lesser Omentum holds the Liver and stomach
• The Mesentery holds the small intestine
• The mesoCOLON attaches the large intestine (colon) to the posterior abdominal wall
• The PERITONEUM, holds PERson's Intestines To Nearest wall.

Oh! Curling turns my Stomach Inside Out

This is what a housewife might say in reaction to her husband's sports selection, but it is a student's way of knowing the 3 layers of muscle around the stomach. The layers are: Oblique, Circular, Longitudinal from inside to outside.

PPL's Tonsils

People (PPL for short) have 3 tonsils: Pharyngeal, Palatine, and Lingual.

Digestive Juices

Bile Breaks fat into Blobs.
Chief stomach enzyme is Pepsin ... remember Geronimo drinking Pepsi to help his digestion.
Parietal cells Produce Acid, Release Intrinsic factor, ET AL.

Causes of blood in the urine:

Given to me a few years back when I was in paramedic school, the six causes of blood in the urine: pooh poohTT -- Stones, Hematological Disorder, Infection, Tumor, Tuberculosis, Trauma.

Cell Biology

Charlie Foster and the Hot Blooded Whore

I learned the 8 functions of blood by the acrostic Old Charlie Foster Hates Women Having Dull Clothes for Oxygen, Carbon dioxide, Food, Heat, Waste, Hormones, Disease, and Clotting but I thought it would be easier to recall if I used the first few letters of each word to make a new sentence. Thus: Waste Ox Cart Food Disease makes Clot in Heated Whore. Of course, I related the hormones to "the whore moans".

Quick Blood / Cardio facts

• Tricuspid valve is in The Right Inside part of the heart.
• Mitral is on Left side.
• B Cells Bite virus, T Cells Torpedo sick cells.
• You need more white blood cells after an immemorable weekend right? Then remember Lying Nude in Basement Early Monday has every white blood cell mentioned: Lymphocytes, Neutrophils, Basophils, Eosinophils, and Monocytes.

Centrioles

Centrioles are useful organelles which play a key role in cell division, namely pulling the chromosomes apart. Centrioles are ropes made of 9 groups of 3 fibres, a 9+3 arrangement. How to remember this? Count the number of letters in "centriole", then count the syllables. You should get 9 and 3.

Into Insulin

Insulin gets sugar Into cells. Without insulin, a person can die from lack of sugar. Romans noticed bees attracted to the urine of diabetics and coined the term "diabetes" to describe the overflow of sugar. There are actually two forms of diabetes: insipidus and mellitus, and are not related. D. insipidus is characterized by excessive and watery urine production and is due to low anti-diuretic hormone level, often caused by a tumor at the hypothalamus. D. mellitus is characterized by high volumes of sugary urine caused by low levels of insulin due to faulty pancreas. Physicians used to tell the difference between the two types of diabetes by dipping a finger into the patient's urine and tasting it -- if it was sweet, he had mellitus.

Tubules & Filaments

Eukaryotic cells are held together by microtubules, microfilaments, and intermediate filaments. I find it easy to remember what each does by matching key letters in each term with their respective duties. For example, Microfilaments are made of Actin, Move Food into MICROvilli, are responsible for Amoebal Movement, Cytoplasmic Streaming, and Muscular Contraction, and they Move Fast. Microtubules on the other hand, are made of TUBulin, Move Slowly, and make the Chromosome fibres.

La Jeune Fils & cell junctions

A Frenchman gawking at a young lady dressed in form-fitting jeans might say Des Tight Gaps and REALLY be thinking about the three types of cell junctions: Desmosome, Tight, and Gap. Desmosome junctions, like good blue jeans, will stretch and are found in the lungs amongst other sites. Tight junctions are useful for containing liquids and make up much of the GI tract. Gap junctions allow cytoplasm exchange between cells and help smooth muscle fibres contract in sequence.

Meiosis Explained

"Meiosis" comes from the Greek "to reduce". Meiosis is the process of reducing the number of chromosomes by half. Without this crucial step in the formation of gametes, our cells would burst with DNA. The goal of meiosis is to make egg and sperm cells with half the number of chromosomes (23 instead of 46) so the egg and sperm can produce a zygote with 46 chromosomes instead of 92. Meiosis appears to be mitosis happening twice without the G1, S1, G2 phases, thereby splitting the chromosomes in half before they replicate. The reduced number of chromosomes is called the haploid state.
In human sperm and egg manufacture, meiosis occurs much as mitosis, but instead of entering interphase after the cell splits, it swings back into prophase and runs through the process again and ends with two daughter cells, each holding 23 chromosomes (the haploid state). Ovum production is slightly different, producing only one ovum, whereas spermatogenesis makes four sperm cells. The difference occurs in telophase I, where the ovum shoves 23 chromosomes into a bud and gets rid of it (women, they hate competition!).

Skin and Tissues

I made up a mnemonic for the layers of the epidermis that worked for me. I started on the outside and worked my way in. This one uses the first 3 letters method: Cora Lucille's Granny Spins Baseballs are Corneum, Lucidum, Granulosum, Spinosum, Basele. Of course, you have to know that "Stratum" goes before each of the words. That part is easy.
Using the 3 first letter method for cranial bones: Ethel, the Parakeet, is Temporarily Occupied in Front of the Sphinx. Ethmoid, Parietal, Temporal, Occipital, Frontal, Sphenoid.
Another 3 first letter method for the cranial sutures: Saggy Lambs Squash the Coroner. Sagittal, Lambdoid, Squamous and Coronal.
Keep up the good work and the great page!

Reproduction

Anna has Large Breasts

I recall the mitotic phases of a cell easily by reciting "I Proposed Marriage to Anna by Telephone before I Sighted her Cleavage". That of course indicates the mitotic phases: Interphase, Prophase, Metaphase, Anaphase, and Telophase, and includes Cytokinesis (sighted) and cell Cleavage.

Understanding DNA/RNA

Although DNA and RNA are both nucleic acids, they do different jobs in the cell. Just remember that DNA Delivers the blueprint, RNA Reads it. Also, transfer RNA (tRNA) molecule is shaped like the letter T.

Mitosis & Meiosis

Easy way to tell the difference between the two types of reproduction at the cell level: mitosis makes Identical Twins, meiosis makes Egg and Sperm.

Brain Physiology

Memories of Girls' Bodily Parts

If you remember girls by their limbs, hip & the anus, hip & kitty, and ass, then you have the four memory centres: limbic, hypothalamus, hippocampus, association areas. BTW, memories are encoded at the neural synapses, usually by acetylcholine. The three key neurotransmitters of the limbic system are dopamine, norepinephrine, and serotonin ... remembered as Limb Donors.

Proprioception

Proprioception, the ability to discern feedback from exertion, is located in the Post-Parietal Sensory cortex. (see how the sounds of proprioception are in post-parietal sensory?)

Brain is a Mystery

The six parts of the brain are a mystery -- murder mystery -- with clues hidden all over, some backwards, some misspelt. We have murder spelt backwards (cerebrum) and skeletons in the celler (CEREbeLLum controls skeletal coordination). There's a detective PONdering M.O. (pons, medulla oblonga), poisoned mulleb wine (in cerebellum), and someone will die before long (Diencephalon), probably some dyslexic dim-brain (mid-brain). Furthermore, forensics have discovered "brain stem" is made up of letters from midBRAIN, pons, and Medulla oblonga. As well, C+D+E=F because Cerebrum + Diencephalon = Forebrain.
In reality, the 6 parts of the brain are: cerebrum, diencephalon, midbrain, pons, medulla oblongata, cerebellum. The major groups are forebrain (the most visible part), the brain stem (three parts piled atop the spinal cord and within the centre of the brain), and the cerebellum hanging off the back.

Maybe Cleopatra had No Brain?

Brain Cells Defended by ASP means the six valiant defenders of the cephalon are Blood-brain barrier, Cerebral spinal fluid, Dura mater, Arachnoid layer, Skull, and Pia mater.

Miscellaneous Brain Facts

• Groups of nerve cell bodies are nuclei if they're in the CNS, and ganglia if in the peripheral nervous system. I remember the nuclei are in the CNS because they both have the letter C.
• Grey matter is central to white matter in the spinal cord, because the white stuff is fat wrapped around and protecting the grey nerves.
• What's the significance of glial cells? They nourish neurons, keep them from falling down, and provide tunnels for axons to route. In another perspective: Albert Einstein's brain had 30% more glial cells than average.
• Four types of glial cells are ependymal, astrocytes, oligodendrocytes, and microglia. The mnemonic phrase is Every place to exchange gas Owes Money.

Muscles

Horny Office Temps

Six factors triggering smooth muscle contraction are oxygen, temperature, ions, hormones, stretch, and acid level (pH). The acronym is "SHIP TO" but the mnemonic phrase is much better: Office Temp's Eye On Whore Stretching Ass. Notice ion is encoded as eye on in this example.

Crossbridge Cycle

The most basic part of the functional muscle is the cross bridge site where muscular contractions occur. The process of myosin heads attaching to actin, bending, then releasing takes four steps: ready, coupling, bending, letting go. A different chemical triggers each step thusly: hydrolysis makes Ready; Calcium ions cause the Coupling; ADP bends the myosin head; ATP lets go. Sounds like a new dance to me.

Calico Cats' Calm Milk

"Calico Cats' Calm Milk" is the pathway of smooth muscle contraction: Calcium Cation attaches to Calmodulin, which binds to Myosin Light Kinase.

Eye and Vision

Eyeball parts

• The sclera, choroid layer, retina and vitreous humor (SCRV) + eyeballs + outer layer add up to: SCREW your eyes out
• The lens, iris, pupil, cornea, aqueous humor, and ciliary body can be summed up in Len and Iris Acquire Puppies in the Corn Silk ... which is an old-fashioned way of saying they're screwing like dogs in the cornfield.
• Fovea, the part of the retina most densely packed with cones, is almost an acronym FOr Very Acute vision
• The cells of the retina -- rods, cones, ganglion, polar bodies -- are illustrated by Rods protected by a Gang of Lions and Polar Bears

Quick Auditory Senses

• The four outer ear parts -- pinna, lobe, helix, meatus -- are easily expressed by a phrase of a lover turning on his girl He licks her helix like a lover pining for meaning
• Middle ear parts -- tympanic membrane, ossicles, eustachian tube, oval and round windows -- are best compiled as Tim Observed Eunice's Tube from two Windows
• Inner ear pieces -- cochlea, sacculus, utriculus, semi-circular canals, 8th cranial nerve -- are summed up in the phrase 8th Nervember, I dropped my cock, my sack, and uterus into the semi-circular canal
• Cochlea sections -- vestibular, tympanic & cochlear canals, basilar membrane, organ of Corti -- might be remembered by thinking of Organ of Corti plays Bass Notes on CTV channel if you admit that channel is another word for canal ... CTV (Canadian Television) are the cochlea, tympanic and vestibular canals, bass notes is basilar membrane, and the organ is the organ of Corti of course.

Hormones

• 8 major hormones from the pituitary gland spell GOAT-FLAP: gonadotropic, oxytocin, anti-diuretic, thyroid stimulating, follicle stimulating, leuteinizing, adrenocorticotropic, prolactin.
• The pituitary gland has two lobes: anterior and posterior. 6 of the preceding hormones come from the anterior lobe; oxytocin and anti-diuretic are secreted from the posterior one.
• The adrenal CORTex produces CORTisol, as well as androgens and aldosterone.
• The adrenal Medulla secretes stress hormones Epinephrine and Norepinephrine and, as all women know, men are a source of stress, so it is no surprise that medulla-epinephrine-norepinephrine make the acronym MEN.
• Adrenal Cortex hormones start with either of letters A, C -- just like adrenal cortex. They are: androgen, aldosterone, cortisol.
• Ovaries are RIPE with hormones: relaxin, inhibin, progesterone, estrogen make the acronym RIPE.
• Testes make TIM strong: "t.i.m." is acronym for the 3 hormones secreted by testes: testosterone, inhibin, and Mullerian-inhibiting hormones.
• Pancreas makes PIGS: Pancreatic polypeptide, Insulin, Glucagon, and Somatostatin hormones.
• Some secret gasses choke gipsy represent the 5 hormones of the (where do you think gas comes from?) gastrointestinal tract: somatostatin, secretin, gastrin, cholecystokinin, glucose-dependent insulinotropic peptide (GIP).
• Melatonin makes penis pineal? Melatonin secreted from pineal gland represses sex drive.
• A Hypocritical Gun-Running Hero goes to Pit to release Long Hard Fish, but is turned off the the smell of Estrogen. That was the story of the hypothalamus secreting GnRH (Gun-running hero) to stimulate the Pituitary gland into releasing LH and FSH. This process is regulated by the levels of estrogen.
• Products of the adrenal cortex, from outer to inner layer: "Salt, sugar, sex; the deeper you go, the sweeter it gets." (Salt=aldosterone, sugar=glucocorticoids, sex=sex hormones)
• To remember how osmosis works, remember that "Particles suck." Thus, tonicity (hypertonic, hypotonic) refers to concentration of particles, and water always goes toward the area of more particles. (thanks to Hallie Ray, Science Department, Rappahannock Community College Warsaw, VA)

Metabolic Rates

I came up with a rhyming verse that helps me remember how our bodies get warm.When we feel cold, the hypothalamus reacts by sending TRH to the pituitary gland, which sends TSH to the thyroid, which secretes T3Tr to reach the mitochondria, wherein the glycolytic pathway consumes more energy and consequently the Electron Transport System consumes more oxygen ... and we get warmer. A more easy way to remember:

O Cold Hippo in the Pit
Thy Sugar Eats
Makes Carbon and Heats

Keywords: Hippo (hypothalamus), Pit (pituitary), Thy (thyroid), Sugar (glycolytic pathway), Eats (ETS), Carbon (carbon dioxide).

Organs

Better than Murder …

While working to uncover a hidden acrostic in the list of bodily organ systems, I strung out the first letters of the 10 and immediately picked out MURDER, but had the letters N, I, C, I left over and did not want to suggest MURDER NICI . Then, I wrote out the first three letter of each and managed to create two phrases which are easy to recall and make remembering the ten systems a cinch! Ergo:

Sir: I'm nervous about reproducing with the rest. Uri must dig into the end.

The organ system names buried within the phrases are (in order): circulatory, immune, nervous, reproduction, respiratory, urinary, muscle, digestive, integumentary, and endocrine. Easy now?

Taxonomy

Carolus Linnaeus (1707-1778) named and classified the various forms of life as a way of seeking order in diversity. He created taxonomy to do this, thus giving headaches to many generations of students. His system of kingdom (plant or animal), phylum (backbone?), class (mammal?), order (carnivore?), family (cat, dog, ape), genus (orangutan or human), species and variety is still used today, only slightly modified from the original. One easy sentence used is King Philip Conquers Our Fifty Grateful States. Two others: King Phillip's Class Of Family Geniuses Specializes in Variety and Kind Phillip's Class Orders Family-sized Gino's Special.
Finally, Z.L. offers this hockey mnemonic: Kings Play Calgary On Friday. Gretzky Scores! Take your pick.
The 5 kingdoms (used to be only 2 or 3) are protoctista, plantae, fungi, monera, animalia. I embedded them into neurons by: Protecting Plants is Fun, Mon Ami, which sounds like a slogan for a French environmental activist group.