The three germ consiting of Ectoderm, mesoderm and endoderm give rise to all the organs and structures in the body. The list of structures developed from 3 primitive germ layers in given below.

Developing embryo

Skin Ectoderm-

• Epidermis, hair, nails,
• Cochlear duct, semicircular ducts,
• Enamel of tooth,
• Adenohypophysis,
• Lens of eye,
• Parotid gland,
• Mammary gland,
• Epithelial lining of lower anal canal.

Neuroectoderm:

• All neurons within brain and spinal cord
• Retina
• Neurohypophysis
• Astrocytes, Oligodendrocytes

Neural Crest-

• Adrenal medulla
• Ganglia- Sensory , Autonomic
• Pigment cells
• Schwann cells
• Meninges- Pia and arachnoid mater
• Pharyngeal arch cartilage
• Ondontoblasts
• Parafollicular C cells
• Aorticopulmonary septum
• Endocardial cushions

MESODERM-

• Muscle ( Smooth, cardiac, skeletal)
• Extraocular muscles ( Preotic somites)
• Muscles of the tongue( occipital somites )
• Connective tissue, dermis of skin
• Bone, cartilage
• Blood and lymph vessels
• Heart
• Adrenal cortex
• Spleen’Kidney’Duramater
• Testes and ovaries

Notocord- Nucleus pulposus

ENDODERM-

1. Epithelial lining of Gastrointestinal tract, Trachea, bronchi, lungs
2. Biliary apparatus
3. Urinary Bladder, Urethra
4. Vagina
5. Auditory tube
6. Middle ear cavity
7. Parenchyma of :- Liver, Pancreas, Submandibular glands, Sublingual gland,Thyroid,Parathyroid

Objective 1:

• To list the important causative agents of meningitis.

TYPES OF MENINGITIS

• Acute Pyogenic Meningitis
• Aseptic Meningitis
• Chronic Meningitis
  • Tuberculous
  • Fungal
  • Syphillitic
  • Protozoal
  • Helminthe

Causative agents of acute pyogenic meningitis

• Neonates
– Escherichia coli
– Group B streptococci
– Listeria monocytogenes
– Streptococcus pneumoniae

• Children
– Neisseria meningitidis
– Streptococcus pneumoniae,
– Haemophilus influenzae

• Adults
– Streptococcus pneumoniae,
– Neisseria meningitidis

• Elderly
– Listeria species

Causative Agents of Aseptic meningitis

• Common:
- Enteroviruses
- Herpes simplex virus 2 (HSV 2)
- Arthropod borne viruses (Tickborne, West Nile, Murray Valley, Japanese B)
- HIV (Human Immunodeficiency Virus)

• Less common
- Varicella zoster virus (VZV)
- Epstein Barr virus (EBV)

Causative Agents of Chronic Meningitis

Tuberculous meningitis

• Mycobacterium tuberculosis

Syphillitic meningits

• Treponema pallidum

Fungal meningitis

• Cryptococcus neoformans (most common in HIV patients)
• Candida albicans
• Mucor species
• Aspergillus fumigatus
• Coccidioides immitis
• Histoplasma capsulatum
• Blastomyces dermatitidis

Protozoal

• Toxoplasma gondii
• Trypanosoma
• Acanthamoeba

Helminthes

• Taenia solium

Objective 2:

• To outline laboratory diagnosis of bacterial meningitis.

Specimens

• CSF
• Blood
• Sample
• Nasal swab
• Peticheal lesions
• Autopsy

A. Examination of CSF

Macroscopy
• CSF is cloudy under increased pressure and blood may be seen.

CSF is centrifuged and following methods are used:

• Microscopy
• Culture

Microscopy

Unstained preparations: wet mounts

Stained smears:

• Common stains: Gram stain, Ziehl-Neelsen stain
• Fluorescent dyes: Acridine orange, Auramine rhodamine

Gram stain (left) and ZN stain (right)

Culture

Culture Media

• Enriched solid media- blood agar, chocolate agar
• Selective solid medium- MacConkey agar
• Robertson Cooked meat broth (for anaerobes)

Steps:

• CSF inoculated in culture media
• incubation at 35-36°C under 5-10% CO2
• Colonies appear after 18-24 hours, identified by morphology and biochemical reactions.

B. Blood culture

• incubated for 4-7 days, with daily subcultures

C. Nasopharyngeal Swab

• Useful for detection of carriers
• Done without contamination with saliva

D. Petechial lesions

Menigococci may be demonstrated by microscopy and culture

E. Autopsy

• Specimen from meninges, lateral ventricles, or surface of brain and spinal cord
• Within 12 hours of death of patient
• Smear or culture

Biochemical tests

• Catalase test
• Oxidase test
• Indole test
• Urease test
• Coagulase test
• Citrate Utilization test
• Triple sugar iron agar

Agglutination test:

• Direct slide agglutination test with specific antisera
• Latex agglutination test
• Immunoflourescence test
• Other rapid identification methods
• Molecular diagnosis – PCR test

Various changes in Acute Pyogenic Meningitis:

References:

• Textbook of Microbiology
• Diagnostic Microbiology

Prepared and Presented for Correlation Seminar in Kist Medical College by:

The posterior inferior cerebellar artery also known as PICA is the largest branch of the vertebral artery, passes on an irregular course between Medulla and Cerebellum.  It is one of the 3 major arteries supplying  the cerebellum. It supplies the posterior part of inferior surface of Vermis, Central nucleii of Cerebellum and undersurface of Cerebellar hemisphere.It also supplies  Medulla ( branches of PICA along with medullary branches of Vertebral artery) and Choroid Plexus of 4 th ventricle.

Cause :-

• It results from thrombosis of Posterior Inferior Cerebellar Artery.
• Causing lateral part of the medulla oblongata to infarct.
• The most commonly affected artery is the vertebral artery, followed by the PICA, superior middle and inferior medullary arteries.

Lateral Medullary syndrome of Wallenberg

Signs and Symptoms that are Characteristic of Wallenberg Syndrome are-

1. Dysphagia and Dysarthria ( Due to paralysis of Ipsilateral palatal and laryngeal muscles- Innervated by Nucleus Ambiguus)
2. Analgesia and Thermaesthesia on the Ispsilateral side of the face ( Due to lesion of Nucleus and Spinal tract of Trigeminal nerve)
3. Vertigo, Nausea, Vomiting and Nystagmus. ( Lesion of Vestibular nucleii)
4. Ipsilateral Horner Syndrome ( due to lesion of Descending Sympathetic fibres)   Mnemonic- “Horny PAMELa” for Ptosis, Anhydrosis, Miosis, Enophthalmos and Loss of ciliospinal reflex
5. Cerebellar Symptoms and Signs-

• • Cerebellar Ataxic/ Drunken Gait
  • Dysdiadochokinesia ( unable to perform quick alternative repeated actions like pronation/supination)
  • Pendular knee jerk
  • Nystagmus
  • Dysmetria
  • Intention Tremor ( Tremor increases as fingers arrive the target)
  • Hypotonia
  • Rebound phenomenon
  • Scanning speech

are the most popularly used antibiotics. They are  any antibiotic agent that contains a β-lactam chain in the molecular structure. Penicillin is the prototype drug and once was a cure for almost anything. Sir Alexander Fleming discovered Penicillin. It was a miracle discovery in history of Mankind.

Sir Alexander Fleming Discovered Penicillin

Mechanism of Action:

-          Interfere with the synthesis of bacterial cell wall

-          Inhibit transpeptidases so that cross linking does not take place

-          When susceptible bacteria divide in the presence of it- cell wall deficient forms are produced resulting in the lysis of bacterial cell

-          Peptidoglycan cell wall is unique to bacteria and it is non toxic to man

-          Gram positive bacteria have higher susceptibility to PnG

Penicillin G (Benzyl Penicillin):

-          Narrow spectrum; gram positive

-          Majority of gram negative bacilli, M.tuberculosis, ricketsiae, chlamydiae, virus insensitive

-          Resistance:

1. Inherent: PBPs located deeper under lipoprotein where PnG is unable to penetrate
2. Penicillinase: opens the beta lactam ring
3. Penicillin tolerant but not penicillin destroying like pneumococci

-          Pharmacokinetics:

1. Acid labile: gastric acid
2. Low oral absorption and rapid and complete absorption from i.m site
3. Plasma t1/2  30 minutes
4. Poor CSF  and serous cavity penetration but increased in inflammation
5. Rapid renal excretion (GFR-10 % and rest tubular secretion)
6. Tubular secretion blocked by Probenecid: higher and longer lasting plasma concentration

-          Preparation and Dose:

1. Sodium Penicillin G injection
2. Repository Penicillin G injection
   1. Procaine Penicillin G
   2. Benzathine Penicillin G

-          Adverse Effects:

1. Local irritancy and direct toxicity: pain at im site, nausea, thrombophlebitis, mental confusion, muscular twitchings, convulsions, bleeding, hallucinations, CNS stimulation
2. Hypersensitivity: Urticaria, fever, wheezing, edema, serum sickness
3. Superinfections
4. Jarisch Herxheimer reaction

Semisynthetic Penicillins:

1. Acid resistant alternative: Phenoxymethyl penicillin (Penicillin V)
2. Penicillinase Resistant: Methicillin, Cloxacillin
3. Extended Spectrum:
   1. Aminopenicillin: Amoxycillin, Ampicillin, Bacampicillin
   2. Carboxypenicillin: Carbenicillin, Tircarcillin
   3. Ureidopenicillin: Poperacillin, Mezlocillin
   4. Beta- lactamase inhibitor: Clavulanic acid, Sulbactam, Tazobactam

Classification

Family: Neisseriaceae
Genus: Neisseria
Species: Neisseria Meningitidis

Morphology

• Gram negative diplococcus (paired)
  

  Neisseria Meningitidis

• Size: 0.6-0.8 μm
• Bean shaped
• Non-motile
• Aerobe
• Encapsulated

Colony characterisitics

• Color: Bluish grey
• Shape: Round
• Size: About 1mm
• Surface: Smooth
• Elevation: Convex
• Opacity: Transluscent
• Consistency: Butyrous

Biochemical Properties:

• Oxidase positive
• Catalase positive
• Ferments glucose and maltose with acid production
• Gamma-glutamyl aminopeptidase positive
• Production of Deoxyribonuclease (DNAse)
• Nitrate negative
• Doesn’t ferment lactose, sucrose and fructose
• Colistin resistant

Serogroups

N. Meningitidis has been divided into atleast 13 serogroups on the basis of specificity of capsular polysaccharide antigens. These are A,B,C,D,X,Y,Z,W 135,29E,H,I,K and L. Serogroups A,B,C,X,Y,W 135 are most commonly associated with meningococcal disease.

Virulence Factors

• Adhesion factors : Pili for adhesion to mucosa of oropharynx and meningeal tissue
• Capsule : Antiphagocytic
• Lipopolysaccharide : Endotoxin
• IgA proteases : cleaves IgA protecting organism from effects of secretory IgA

Epidemiology

• Natural habitat and reservoir : Mucosal surfaces of the human nasopharynx, urogenital tract and anal canal
• Nasopharyngeal carriers : approximately 5-10% adults are asymptomatic carriers (may reach 90% in close communities)
• Modes of infection: Direct contact or respiratory droplets from the nose and throat of infected people

Pathogenesis (Steps)

1. Inhalation of contaminated droplets
2. Adherence of organism to nasopharyngeal mucosa
3. Local invasion and spread from nasopharynx to meninges through blood stream
4. In meninges, organsims are internalised into phagocytic cells
5. They replicate and migrate to subepithelial spaces
6. Incubation period : 3-4 days

Clinical Features

• Febrile illness : Mild and self limiting
• Pyogenic meningitis : High fever, stiff neck, Kernig’s sign, severe headache, vomiting, photophobia, chills
• Meningiococcal speticemia : acute fever with chills, malaise, prostation, Waterhouse-frederichsen syndrome, DIC
• Other Syndrome : Pneumonia, arthritis, urethritis, respiratory tract infection

Prophylaxis

Meningococcal septicemia

a. Chemoprophylaxis :

• Rifampicin
• Minocycline
• Ciprofloxacin

b. Vaccination:

• A vaccine containing capsular polysaccharide of serotypes A and C : for infants below 2 years
• A quadrivalent vaacine constituted by polysaccharides of serotypes A,C,Y and W-135 : for children and adults

Laboratory Diagnosis

a. Specimen:

• CSF
• Blood

b. Examination of CSF:

• Increased Pressure
• Turbid

The collected CSF is divided into 3 portions (for microscopy, for biochemical tests and for culture)

Microscopy:

• Gram stained smear of CSF deposit commonly shows Gram negative intracellular diplococci.
• White cell count increases to several thousand per cubic mm with 90-99% PMNs.

Biochemical tests:

• Glucose is markedly diminished
• CSF protein is markedly raised

c. Culture:

CSF:

• Inoculated into chocloate agar
• Incubated at 37c in 5-10% Carbondioxide and high humidity
• After 24 hours bacterial colonies appear
• The organism is tested for biochemical and agglutination reaction

Blood:

• Blood culture is positive in over 40% cases of meningiococcal meningitis

Other Cultures:

• Nasopharyngeal swab
• Skin lesions
• Joint fluid
• Tracheal aspirate
• Urethral discharge

d. Detection of antigen:

For Detection of Meningiococcal DNA

• Polymerase Chain Reaction (PCR)

For detection of soluble polysaccharide antigen

• Counter current immunoelectrophoresis (CIEP)
• Latex agglutination test

e. Serogrouping

Introduction:

• Nervous system is one of the earliest systems to begin development and the last to be completed after birth.
• The entire nervous system develops from the ectoderm.
• Ectoderm forms the neural plate during 3rd week of development.
• Neural Groove forms in the midline of the neural plate ,either side of which are the neural folds. Groove continues to deepen until about week 4. Neural folds begins to fuse and form neural tube.
• Neural tube consists of 2 openings : cranial (anterior) neuropore and caudal (posterior neuropore)
• The cranial neuropore closes earlier than the caudal neuropore.
• The enlarged cranial part of the neural tube forms brain and the caudal tubular part forms the spinal cord.
• A population of cells at the edge of the neural plate that lie dorsally when the neural tube fuses forms the neural crest and it lies dorsal to the neural tube, as a pair of streaks.

Derivatives of neural crest:

• Adrenal medulla
• Pia and arachnoid sheath
• Dorsal root ganglion
• Craniofacial skeleton
• Melanocytes
• Schwann cells
• Odontoblast
• Thyroid parafollicular cells
• Symphatetic ganglia
• Parasymphatetic ganglia

Fates of cranial part of neural tube:

1. Forebrain vesicle –> Prosencephalon

• telencephalon – cerebral hemisphere
• diencephalon – thalamus, hypothalamus, epithalamus

2. Midbrain vesicle –> Mesencephalon: Tectum, tegmentum, substantia nigra, crus cerebri

3. Hindbrain vesicle –> Rhombencephalon

• Metencephalon – pons and cerebellum
• Myelencephalon – medulla oblongata

Formation of basal and alar plate:

• The wall of the neural tube consists of a single layer of pesudostratified columnar epithelial cells, called matrix cells.
• Matrix cells rapidly divide and form neuroblasts and glioblasts.

Neuroblasts give rise to following layers:

• Mantle (intermediate zone)
• Marginal (Layer external to mantle)

Mantle further forms 2 areas separated by sulcus limitans:

• Basal lamina or plate (ventrally) – motor
• Alar lamina or plate (dorsally) – sensory

Glioblasts give rise to:

• Astrocytes
• Oligodendrocytes
• Microglial cells
• Ependymal cells (arise from matrix cells that line neural tube)

Development of spinal cord:

• Neuroblasts of basal plate (motor) forms motor cells of anterior gray column and their axon forms anterior nerve root of spinal nerves.
• Neuroblasts of alar plate (sensory) forms sensory cells of posterior gray column and interneurons.
• Neural crest cells migrate posterolaterally on each side of spinal cord and give rise to dorsal root ganglia and dorsal root of spinal nerves.
• Progressive growth of basal plate on either side forms anterior median fissure
• Progressive growth of alar plate on either side forms posterior median septum and central canal (form lumen of neural tube)

Medulla oblongata:

• Develops from myelencephalon
• As a result of expasion of 4th ventricle, alar plates come to lie lateral to basal plate.
• Neurons of basal plate form motor nuclei of cranial nerves (IX,X,XI,XII) in medulla.
• Neurons of alar plate form sensory nuclei of cranial nerves in medulla (V,VIII,IX,X) in medulla.
• Remaining cells of alar plate migrate ventrolaterally to form olivary nuclei.

Pons:

• Develops from ventral part of metencephalon.
• It has also cellular contributions from the alar part of the Myelencephalon.
• Basal plate forms : the motor nuclei of cranial nerves (V,VI,VII).
• Alar plate forms : Sensory nucleus (V,VII), Vestibulo-cochlear nuclei (VIII) and pontine nuclei.
• Axons of the pontine nuclei go to the developing cerebellum of the opposite side (Rhombic lip) & form transverse pontine fibers and middle cerebellar peduncle.

Cerebellum:

• Develops from dorsal part of metencephalon.
• On each side, alar plate bends medially to form the rhombic lip
• Right and left rhombic lip grows caudally and fuses with across midline forming cerebellum
• At 12th week: small midline portion differentiates into vermis and 2 lateral portion differentiates into cerebellar hemispheres
• Migration of neuroblasts from matrix cells in ventricular zone to cerebellum leads to formation of cerebellar cortex.
• Neuroblasts remaining close to ventricular surface forms cerebellar nuclei (d,e,g,f = dentate, emboliform, globose, fastigii)

Midbrain:

• Develops from mesencephalon.
• Cavity of mesencephalon remains narrow to form cerebral aqueduct.

Basal plate forms:

a) Motor nuclei of the 3rd & 4th cranial nerves
b) Red nuclei
c) Substantia nigra
d) Reticular formation

• The marginal zone of basal plates on each side enlarges to form basis pedunculi (The descending motor tracts are situated in that region – Cortico pontine, corticobulbar & corticospinal tracts)
• The 2 alar plates & the roof plate forms the Tectum.
• The alar plate forms the sensory neurons of the superior & inferior colliculi.

CEREBRAL HEMISPHERE:

• Starts developing at 5th week.
• Thickening of the walls lead to reduction of intraventricular foramen.

Cerebral hemispheres grow & expand:

• Anteriorly : Form frontal lobes (1st)
• Laterally & superiorly : Parietal lobes (2nd)
• Posteriorly & inferiorly : occipital & temporal lobes (Last)
• Falx cerebri and flax cerebellum is formed by the condensation of mesenchyme between hemispheres.

Cerebral cortex:

• Develops from telencephalon.
• Migration of cells from mantle layer to marginal layer–>surface expansion–>cortex folds on itself–>formation of sulci and gyri
• By development cortex are of 3 types: hippocampal, pyriform and neocortex.

At the 12th week, cortex become very cellular due to migrating neuroblasts; different areas of the cortex will show specific cell types due to the influence of the ascending & descending tracts

• Motor cortex : Pyramidal cells
• Sensory areas : Granular cells

Corpus striatum:

• Develops from telencephalon.
• Remaining cells of mantle layer forms caudate nucleus and lentiform nucleus.
• Many axons from ascending & descending tracts that pass between the thalamus & caudate nucleus medially and lentiform nucleus laterally as a bundle forms internal capsule.
• Similarly, cortical projections lateral to lentiform nuclei forms external capsule.

Thalamus and hypothalamus:

• Develops from diencephalon.
• Diencephalon is divided by epithalamic sulcus and hypothalamic sulcus into 3 surfaces.
• Part above epithalamic sulcus forms epithalamus (habenular nuclei and pineal body)
• Middle part forms the thalamus.
• Part below hypothalamic sulcus forms hypothalamus.

Commisures:

• Lamina terminalis (The cephalic end of the neural tube) forms a bridge between the 2 cerebral hemispheres. Optic chiasma is formed by inferior part of lamina terminalis.
• Anterior commissures : 1st commissure to develop. It connects olfactory bulbs of the temporal lobes on either side with each other.
• Fornix : 2nd commissure to develop. Connects hippocampus in each hemisphere
• Corpus callosum: 3rd commissure to develop. It connects frontal and parietal lobes of both hemispheres.
• The remaining of the lamina terminalis (Lies between the corpus callosum & the fornix) form the septum pellucidum.

Development of Eye:

Development of eye

• Outpouching of forebrain vesicle forms optic vesicle (3rd week).
• The optic vesicles come into contact with the epithelum and induce the epidermis. The epithelium thickens to form the lens placode.
• The lens differentiates and invaginates until it pinches off from the epithelium. The lens acts as an inducer back to the optic vesicle to transform it into the optic cup and back to the epidermis to transform it into the cornea.
• The optic cup then delaminates into two layers: The neural retina and the retinal pigment epithelium.
• The periocular mesenchyme migrates in during the formation of the optic cup and is critical for the induction of the retinal pigment epithelium and the optic nerve.

Antiviral

CLASSIFICATION:
1. Anti-herpes virus: Idoxuridine, acyclovir, valacyclovir, famciclovir, ganciclovir, forscarnet
Except forscarnet which is an inhibitor of DNA polymerase and reverse transcriptase, others are purine and pyrimidine anlaogues.

2. Anti-retrovirus:
a. Nucleoside reverse transcriptase inhibitors (NRTIs): Zidovudine (AZT), Didanosine, Zalcitabine, Stavudine, Lamivudine, Abacavir
b. Non-nucleoside reverse transcriptase inhibitors (NNRTIs):Nevirapine, Efavirenz, Delaviridine
c. Protease inhibitors: Ritonavir, Indinavir, Nelfinavir, Saquinavir, Lopinavir

3. Anti-influenza virus: Amatidine, Rimantadine

4. Nonselective antiviral drugs: Ribavirin, Lamivudine, Interferon alpha

General Mechanism of Action of Nucleoside Analogues:
1. Taken up by cells
2. Converted by viral and cellualr enzymes to the triphosphate form
3. The triphosphate form inhibits:
a. DNA polymerase
b. Reverse transcriptase
c. RNA polymerase
4. Or it may get incorporated into growing DNA leading to abnormal proteins or breakage.

ANTI-HERPES VIRUS DRUGS:

1. Acyclovir and Valaciclovir: These are guanine analogues with antiviral activities against Herpes group only.

Mechanism of action:

Acyclovir –viral thymidine kinase–> AcycloGMP –cellular kinases–> AcycloGTP
AcycloGTP performs 2 functions:
a. Inhibits viral DNA polymerase competitively
b. Termination of DNA synthesis by incorporation into DNA

Mechanism of resistance development:
a. Reduced activity of viral thymidine kinase
b. Altered DNA polymerase

Use:
The activity of acyclovir on herpes group:
Herpes simplex type I > Herpes simplex type II > (Varicella-zoster virus = Epstein-Barr virus)
Cytomegalovirus (CMV) are practically not affected.

a. Genital Herpes simplex (type II)
b. Mucocutaneous H. simplex (type I) : remains localized to lips and gums
c. H.simplex encephalitis (type I)
d. H. simplex (type I) keratitis : because of good corneal penetration
e. Herpes zoster
f. Chickenpox

Adverse effects:
a. Topical: stinging and burning sensation
b. Oral: headache, nausea, malaise
c. Intravenous: rashes, sweating, emesis and fall in BP
d. Other toxicities:
i. Renal insufficiency (normalization on discontinuation of drug)
ii. Encephalopathy : tremors, lethargy, disorientation, hallucinations, convulsions and coma

Valaciclovir is an ester prodrug of acyclovir with improved oral bioavailability. It is the drug of choice in herpes zoster.

2. Famciclovir: It is used an alternative to acyclovir for genital or orolabial herpes and herpes zoster.

3. Ganciclovir:
a. Analogue of acyclovir
b. Active against all herpes viruses including CMV
c. CMV can develop ganciclovir resistance by mutation
d. Low oral bioavailability given I.V.
e. Drug of choice for CMV infection in immunosupressed patients (eg. AIDS) : pneumonia, colitis, retinitis

Adverse effects:
a. Bone marrow supression : leukopenia and thrombocytopenia
b. CNS effects: headache, behavioral psychosis, coma, convulsions
c. Rashes, fever, vomiting

4. Idoxuridine and Trifluridine:
a. Topical agent for Herpes keratitis
b. Triflurdine (also for CMV) is better for H.simplex II keratoconjunctivits

5. Forscarnet:
a. Direct inhibitor of DNA polymerase and reverse transcriptase
b. An inorganic pyrophosphate analogue

ADR:
a. Nephrotoxicity (Renal diabetes like condition, acute renal failure)
b. Hypocalcemia, hypokalemia and hypomagnesemia
c. Anemia
d. Tremor, convulsions
e. Phlebitis (administered i.v.)

Use:
a. CMV retinitis and other CMV infections resistant to gancyclovir
b. H.simplex and Varicella Zoster resistant to acyclovir
c. HIV

Also known as

• Dangerous area of face
• Danger area of face
• Triangle of death of face

Definition and description

It approximately covers the area from the corners of the mouth to the bridge of the nose, including the nose and maxilla. The facial vein is the largest vein of the face with no valves. Deep connections of the facial veins include:

• A communication between the supraorbital and superior opthalmic veins.
• With the pterygoid plexus through the deep facial vein which passes backwards over the buccinator.

Veins of face and their deep coneections with the cavernous sinus and the pterygoid plexus of veins

The facial vein communicates with the cavernous sinus through these connections. Infections from the face can spread in retrograde direction and cause thrombosis of the cavernous sinus. This is specially likely to occur in the presence of infection in the upper lip and in the lower lip and in the lower part of the nose. Cavernous sinus thrombosis can be serious and needs to be treated immediately. It is easily treated with high doses of antibiotics given intravenously.

For General Understanding

The blood from this area drains to the back of the head and it also meets up with veins at the base of the brain. From there it goes to the cavernous sinus, where all the blood is received. All the blood vessels from this area drain eventually to the brain. Any infections from this area can cause eye and vision problems, headaches, fever, neck stiffness, etc. It can lead to complications like blindness, paralysis of face, meningitis, sepsis and possibly death.

Points to Remember

• Use a clean tissue to clean something from your nose instead of picking it with fingers. Nasal passage can be cleaned using nasal rinses.
• Instead of plucking your nose hair, use a nose trimmer.
• Do not squeeze or pick the pimples or zits in this area. Use emollient jelly instead.
• Facial piercings may also give problems.

Upper and Lower Motor Neurons

All the neurons contributing to the pyramidal and extrapyramidal systems should be called upper motor neurons (UMN).
The anterior horn cells and the related neurons in the motor nuclei of some cranial nerves are called lower motor neurons (LMN). Axons of these cells give rise to the peripheral motor nerves. These are lowest in position in the motor system and recieve all the inputs from higher centers like medulla, pons, mid-brain and cerebral cortex and transmit the same to the target organs. All impulses for motor activity are to be funelled into them and these are also called final common pathway.

Signs of Upper Motor Neuron Lesions (UMNL)

1. Paralysis or weakness of movements of the affected side but gross movements may be produced. No muscle atrophy is seen initially but later on some disuse atrophy may occur.

2. Babinski sign is present: The great toe becomes dorsiflexed and the other toes fan outward in response to sensory stimulation along the lateral aspect of the sole of the foot. The normal response is plantar flexion of all the toes.

Babinski Reflex

3. Loss of performance of fine-skilled voluntary movements especially at the distal end of the limbs.

4. Superficial abdominal reflexes and cremasteric reflex are absent.

5. Spasticity or hypertonicity of the muscles.

6. Clasp-knife reaction: initial higher resistance to movement is followed by a lesser resistance

7. Exaggerated deep tendon reflexes and clonus may be present.

Signs of Lower Motor Neuron Lesions (LMNL)

1. Flaccid paralysis of muscles supplied.

2. Atrophy of muscles supplied.

3. Loss of reflexes of muscles supplied.

4. Muscles fasciculation (contraction of a group of fibers) due to irritation of the motor neurons – seen with naked eye.

5. Muscle fibrillation (contraction of individual fibers) – detected only by EMG

6. Muscle contracture (shortening of paralyzed muscles)

7. Presence of muscle wasting

8. Reaction of degeneration: When the LMN is cut, a muscle will no longer respond to interrupted electrical stimulation 7 days after nerve section, although it will still respond to direct current. After 10 days, response to direct current also ceases.

Mnemonic for Medical Students

Upper Motor Neuron Lesion vs Lower Motor Neuron Lesion : Difference or comparison between upper motor neuron lesion (UMNL) and lower motor neuron lesion (LMNL)

Mnemonic for basis of difference: STORM Baby
Also remember: In a Lower motor neuron lesion everything lowers

Opioids are among the commonly misused substance by drug abusers around the world. Opioids come in various forms – Heroin , Morphine, Methadone, Coedine, Pethidine, Dihydrocoedeine.

Opioids are a class of drugs derived from the extracts of plant- opium poppy. Used as Analgesics but  most opiates give a feeling of euphoria and a degree of sedation. These side effects are the cause of Abuse of Opioids.

Opioid overdose can be lethal

Clinical Features Of Opiod Intake in body are-
Rapid, intensely presurable experience
Heightened sexual arousal
Increase dose required for same experience within weeks

Withdrawl Symptoms include-
Intense craving , Rhinorrhea, Lacrimation, Yawning, Perspiration, Shivering, Piloerection, Vomiting and diarrhea, abdominal cramps.
Tachycardia, hypertension, mydriasis ( dilation of Pupil ) and facial flushing.

Hallmark Of Opioid Poisoning are-
Respiratory depression – may lead to death
Pin-point Pupil
CNS depression- decresed level of consciousness.
Signs of IV drug misuse like needle tract marks, tattoo.

Severe –
Respiratory depression
Hypotension
Non-cardiogenic pulmonary edema
Hypothermia
Death due to Respiratory arrest and Gastric aspiration
Others- Ventricular Arrhythmia, Conduction defects and heart blocks

Lab Diagnosis Criteria ( CDC)

• Biologic: A case in which opioids are detected in urine, as determined by hospital or commercial laboratory tests. Fentanyl derivatives and certain other synthetic opioids (e.g., oxycodone) might not be detected by routine toxicologic screens.

- OR-

• Environmental: Detection of opioids in environmental samples, as determined by FDA

Management-
1. Clear Airway and provide Respiratory support
2. Supplement increase flow Oxygen administration
- Severe cases Endotrachel intubation may be required.
3. Antidote- Naloxone is the anti-dote for Opioids. Naloxone is given in dose of 0.8-2 mg bolus IV and repeated every 2 minutes until pupil dilates. Opioid overdose is a challenging condition that requires a difficult balancing act between over and under treatment with naloxone. Nalorphine is an alternative. Literature : Naloxone in Opioid Overdose
4. O2 saturation must be monitored .
5. Management of Hypotension.
6. CPAP/ PEEP for ventilator support.

SAY NO TO DRUGS- Medchrome Against Drug Abuse
Warning- Do not take drug without physician’s prescription.