GLUCOSE 6 PHOSPHATE DEHYDROGENASE DEFICIENCY AND HEMOLYTIC ANEMIA

G6PD DEFICIENCY and HEMOLYTIC ANEMIA

G6PD deficiency is a form of inherited disorder (that occurs mostly in males) in which body lacks an enzyme which normally protects RBCs from toxic chemicals.

G6Pd deficiency is commonest enzymopathy of RBCs,

BACK GROUND INFORMATION NECESSARY TO UNDERSTAND THE DISEASE

Applied biochemistry ,red cell enzymes

1.Matured RBCs lack nucleus,mitochondria and ribosomes.

And no tricarboxylic acid cycle and no synthesis of new proteins

2.To maintain integrity –rely on glycolysis

3.Natural decay of enzyme activity  ends the life span of RBC

Energy for RBCs

RBCs require constant energy to maintain biconcave disk form and

hemoglobin in reduced state.

without enrgy RBC lyse,deform

Energy is derived by metabolizing glucose by 2 pathways

1.Aerobic pathway- pentose phosphate shunt

2.via anerobic pathway Embden Myerhof pathway

(Most important is Hexose monophosphate shunt)

Metabolism of glucose

Via hexose monophosphate shunt

By metabolising glucose,ATP is produced

Glucose is metabolized to pyruvate by number of enzymes.(important -Pyruvate kinase)

G6PD-  (Glucose 6 phosphate dehydrogenase ) is the first enzyme which takes part in the above shunt.

The above shunt generates NADPH through the enzyme G6PD

NADPH keeps glutathione(GSSG) in reduced state(GSH)

This GSH protects RBC proteins from oxidative damages;reduced glutathione acts as a scavenger  of free radicles.

In response to oxidant stress normal RBCs produce NADPH

Pathophysiology of Hemolysis

When there is defientG6PD enzyme, NADPH  production is impaired

So,unable to withstand oxidative stress,damage occurs to

 sulph hydryl group of Hemoglobin

and RBC cell membrane causing hemolysis

Note:

·         Oxidative damage occurs due to free radicles  created by conversion of oxy to deoxy HB

and peroxidases created by phagocyting granulocytes

·         Other cells in other tissues have alternative pathways to generate NADPH

·         Enzymes of reticulocytes are very active but as cell ages activity falls.G6PD deficiency worsens as RBCs age .During periods of oxidative stress, hemolysis begins with oldest RBCs and progressively involves younger RBCs depending on severity.As RBCS do not have nuclei, when G6PD degrades,there is no G6PD mRNA to replace it.

BIOCHEMICAL PATHWAY –
THE HEXOSE MONOPHOSPHATE SHUNT

ANEROBIC PATHWAY

PENTOSE PHOSPHATE PATHWAY-Aerobic pathway

Variants of  the enzyme

About 100 variants exist in G6PD  deficiency

Normal type –TypeA and B

Unstable variant found in affected male Africans

 Unstable Variant A called A--

 Reticulocytes in A—have normal activity but declines with age(hemolysis is self limiting)

Variant TypeB—    seen in Mediterraneans ;activity very low,so hemolysis severe.

WHO working group classification

Class I ;  Severely deficient with chronic non spherocytic hemolytic anemia

ClassII;  Severly deficient with acute intermittent hemolysis(G6PD meditteranean)

CLASSIII: Moderately deficient with intermittent hemolysis usually associated with infection or drugs

 ClassIV:   Normal activity(60% -150%)

ClassV:     Increased activity (>150%)   

 TRANSMISSION OF THE DISEASE

Transmission is X linked through a defective G6PD gene located on X chromosome

Mutation of that gene.

Therefore typically affects men

Since this is a X linked gene,prevalence in females –higher but females are usually asymptomatic

Expression of disease occurs in

Hamizygous male and

Homozygous females

(Males possess only one copy of the gene thus they are either normal or G6PD deficient.

Heterozygous females withG6PDD have 2RBC populations;one normal,one withenzyme deficiency)

Affected people are intolerant to oxidative stress ,result is hemolysis

X chromosome and the position of G6PD gene atXq28 locus

.Epidemiology:

About 400 million people affected world wide

Highest prevelance in :

people of African, meditteranian  and Asian heritage

G6PD deficiency confers a relative resistance against plasmodium falciparum

CLINICAL FEATURES   

·         Usually asymptomatic                    

·          In all patients  severity varies

·         Varies from intermittent hemolysis to chronic hemolysis

or sudden life threatening intra vascular hemolysis with loin pain and hemoglobinurea

TYPES OF PRESENTATION

 !. Acute Hemolysis

2. Intermittent hemolysis

#. Chronic mild hemolysis

4. Drug induced hemolysis

5.Favism

6. Neonatal jaundice

7. Congenital non spherocytic hemolytic anemia

1. ACUTE HEMOLYTIC ANEMIA

After remaining asymptomatic

Sudden hemolysis 2-3 days after precipitating factor

Abrupt fall in Hemoglobin to 4 gms /dlrange

In 5-7 days reticulocytes increase and reverse anemia

even without removal of the drug

In Meditteranean type –severe form- hemolysis continues  even after withdrawl of drug.

2. DRUG INDUCED HEMOLYTIC ANEMIA

Occurs with all types

severe in medetteranean and oriental types

In African type –less severe self limiting

Drugs causing hemolysis

Antimalarials-         primaquin,qunine,chloroquine

Anti bacterials-       Sulpha,nalidixic acid,nitrofurantoin chloromycetin,+pyridium

Anti tuberculous-   Para aminosalicylic acid

Anti lepromatous-  Dapsone

Analgesics-            Aspirin,phenacetin

Vitamin K

Methelene blue--- Antitode for meth hemoglobinemia

Certain Chinese medicines

Food s triggering

Fava beans,fava bean products

 Other triggers causing hemolysis

House hold products- Moth balls

Naphthalene containing products

Metabolic precipitant-Diabetic keto acidosis

Severe Hemolysis and acute renal failure and death may occur.

3. FAVISM

Severe hemolysis followed by ingesting  fava beans

Even inhalation of fava pollens

Occurs in Mediterranean group

fava beans

4.INTERMITTENT HEMOLYTIC EPISODES

Provoked by 

Pneumonia.

Hepatitis ,Diabetic ketoacidosis

5.CHRONIC MILD HEMOLYSIS –occurs with some varients

6.NEONATAL JAUNDICE-

Common in meditteranean and oriental group.

Provoked by Vit K

D.D-Rhesus hemolytic disease of new born

7.Congenital  non spherocytic hemolytic anemia

ClassI variant

Defect very severe;normal stress   in circulation cannot be withstood.

New born period itself-anemia &jaundice develop.

Severe cases-neutrophilic defect also associated

NOTE:

In all patients severity varies from clinically inapparent to dramatic life threatening event.

Physical exam during hemolysis shows jaundice and spleenomegaly.

Tests for G6PD  deficiency

1 .Many variants exist in G6PD deficiency (about 100)

2. Old cells hemolyse more thanyoung RBC,since they contain more enzymes

5. G6PD assay Just after hemolysis can be misleading since new normal cell are released into circulation

6. In young cells G6PdD >6PGD.So,G6Pd/6pgd ratio will give correct picture in acute hemolysis.

7 .G6PD/6PGD  ratio help to detect heterozygotes

   Screening tests for G6PD deficiency are available

After initial screening ,select patients for further investigations

Best technique Spectro photometer assay  

If equivocal reassay after few weeks if clinical suspicion exists

More sensitive is Electrophoretic technique.

DIFFERENTIAL DIAGNOSIS for G6PD deficiency

Hemolytic anemia

Sickle cell anemia

Heriditary sphrocytosis

INVESTIGATIONS      

CBC

Reticulocyte count

Urine analysis

LDH/Hepatoglobin

Serum haptoglobin level will reduce in hemolysis ;is an index of hemolysis

Fractionated bilirubin

Blood smear with stains for Heinz bodies They are denatured hemoglobin.within RBCS

G6PD fluroscent Spot test

This test looks for fluorecense of NADPH

In this disease when NADPH is absent ,fluorescence is absent

G6PD spectrophotometry

Genetic test variant

Imaging studies

Abdominal USG shows splenomegaly and gall stones

TREATMENT

Avoid offending drugs and any other precipitating agents

Supportive care(oxygen,bed rest)

In neonatal jaundice phototherapy or  exchange transfusion

Adequate hydration to avoid renal failure

Transfusion

Folic acid

Vitamin E as antioxidant (Efficiecy?)

Splenectomy

 One Significant Complication

Myoglobinuria or hemoglobinuria  from hemolysis can cause Acute Tubular Necrosis
Microscopic exam of urine shows granular casts;

Urine is reddish brown .

Pathogenesis

Heme pigment casts obstruct the tubles,volume depletion and ischemia

FeNa less than  one percent as against typical ATN

This shows that there is tubular obstruction rather than ischemia.

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HEMOLYTIC ANEMIA

HEMOLYTIC ANEMIA

 CAUSES OF HEMOLYTIC ANEMIA

The immediate cause of hemolytic anemia is the early destruction of red blood cells.

Red blood cells are destroyed and removed from the bloodstream before their normal lifespan is over.

causes can be inherited or acquired.

Sometimes,not known.

Inherited Hemolytic Anemias

You can get a faulty red blood cell gene from one or both of your parents.

Different types of faulty genes cause different types of inherited hemolytic anemia.

, in each type, the body makes abnormal red blood cells.

 The defect may involve the hemoglobin, cell membrane, or enzymes that maintain healthy red blood cells.

The abnormal cells are fragile and break down while moving through the bloodstream.

In condition spleen removes the cell debris from the bloodstream.

Conditions causing

Sickle cell anemia (painful occlusive crisis)

Thalassemia

G6 PD deficiency

Acquired Hemolytic Anemias

In acquired hemolytic anemias, the body makes normal red blood cells.

However, a disease, condition, or other factor destroys the cells.

conditions that can destroy the red blood cells include:

 Auto Immune disorders e.g.Lupus,Wiskott-Aldrich syndrome

Infections

 Blood transfusion

Hypersplenism

Infection:E.coli,EB virus,Streptococcus,Typhoid fever

Tumor

Leukemia

Lymphoma

Reactions to medicines –Acetaminophene,penicillin,methicillin,Chlorpromazine.Ibuprofen

interferonAlpha,procainamide.quinine,

Who Is at Risk for Hemolytic Anemia?

Age and sex incidence:all ages and races and both sexes.

 Some types of hemolytic anemia are more likely to occur in certain populations than others.

For example, glucose-6-phosphate dehydrogenase (G6PD) deficiency mostly affects males of African or Mediterranean descent.

 In the United States, the condition is more common among African Americans than Caucasians.

In the United States,sickle cell anemia mainly affects African Americans

SIGNS AND SYMPTOMS OF HEMOLYTIC ANEMIA

The signs and symptoms of hemolytic anemia will depend on

 the type and severity of the disease.

mild hemolytic anemia no signs or symptoms.

More severe cases -many signs and symptoms, and may be serious.

Many of the signs and symptoms of hemolytic anemia apply to all types of anemia

Signs and Symptoms of Anemia

The most common symptom of all types of anemia is fatigue (tiredness).

 Fatigue  becauseof reduced  oxygen carrying capacity  due to fall in RBC count

A low red blood cell count also can causedyspnea, dizziness, headache, coldness in hands and feet, pale skin, and chest pain.

Because of  lack of red blood cells that  heart has to work harder . This can lead to arrhythmia, heart murmur an enlarged heart, Heart failure.

Signs and Symptoms of Hemolytic Anemia

• Jaundice

When red blood cells die, they release hemoglobin into the bloodstream.

The hemoglobin is broken down into the compound  bilirubin, which gives the skin and eyes a yellowish color. urine becomes dark yellow or brown.

• Pain in the Upper Abdomen

Gallstones or an enlarged spleen may cause pain in the upper abdomen.

 High levels of bilirubin and cholesterol (from the breakdown of red blood cells) can form into stones in the gallbladder. These stones can be painful.

The spleen helps fight infection and filters out old or damaged blood cells. In hemolytic anemia, the spleen may be enlarged, which can be painful.

• Leg Ulcers and Pain

In   sickle cell anemia, the sickle-shaped cells can clog small blood vessels and block blood flow. This can cause leg sores and pain throughout the body.

As Reaction to  incompatible blood transfusion:

One may develop hemolytic anemia due to a blood transfusion. Signs and symptoms of a severe reaction to a transfusion include fever, chills, hypotension and shock..

Physical Exam and Investigations

Aim;To Find out how severe the condition is and what's causing it.

Physical  exam includes:

• Checking for jaundice
•  Examine for rapid or irregular heartbeats
• Check for rapid or uneven breathing
• check the size of spleen
• pelvic and rectal exam to check for internal bleeding

Diagnostic Tests and Procedures

Tests to confirm the diagnosis, cause and find the severity.

1.complete blood count(CBC).

2. Also check hemoglobin and hematocrit levels.

.The normal range of these levels may vary in certain racial and ethnic populations.

3.Look at mean corpuscular volume (MCV-.

,MCV is a measure of the average size of red blood cells. (A clue as to the cause of anemia.)

Other Blood Tests

If the CBC results confirm anemia, other blood tests are done  to find out what type of anemia patient has and how severe it is.

Reticulocyte count. A reticulocyte count measures the number of young red blood cells in blood. The test shows whether bone marrow is making red blood cells at the correct rate.

People who have hemolytic anemia usually have high reticulocyte counts because their bone marrow is working hard to replace the destroyed red blood cells.

Peripheral smear.: Some types of hemolytic anemia change the normal shape of red blood cells.

Coombs' test. This test can show whether body is making antibodies (proteins) to destroy red blood cells.

Haptoglobin

 Normlly when red blood cells break down, they release hemoglobin into the bloodstream.

The hemoglobin combines with haptoglobin.

A low level of haptoglobin in the bloodstream is a sign of hemolytic anemia.

Bilirubin, and liver function tests

Hemoglobin is broken down into bilirubin. High levels of bilirubin in the bloodstream may be a sign of hemolytic anemia. High levels of this compound also occur with some liver and gallbladder diseases.

 liver function tests:  to find out what's causing the high bilirubin levels.

Hemoglobin electrophoresis.

 This test looks at the different types of hemoglobin in blood.

 It can help diagnose the type of anemia.

Test for paroxysmal nocturnal hemoglobinuria (PNH).

 In PNH, the red blood cells are missing certain proteins. The test for PNH can detect red blood cells that are missing these proteins.

Osmotic fragility test. To look for red blood cells those are more fragile than normal. These cells may be a sign of hereditary spherocytosis (an inherited type of hemolytic anemia).

Testing for glucose-6-phosphate dehydrogenase (G6PD) deficiency

 In G6PD deficiency, the red blood cells are missing an important enzyme called G6PD

.. Bone Marrow Tests

Bone marrow tests to  show whether bone marrow is healthy and making enough blood cells. The two bone marrow tests are aspiration and biopsy.

bone marrow aspiration:, Removal a small amount of fluid bone marrow through a needle. The sample is examined under a microscope to check for faulty cells.

bone marrow biopsy may be done at the same time as an aspiration or afterward removal ofsmall amount of bone marrow tissue through a needle. The tissue is examined to check the number and type of cells in the bone marrow.

Patient may not need bone marrow tests if blood tests show what's causing hemolytic anemia.

Tests for Other Causes of Anemia

Because anemia has many causes, also tests for conditions such as:

Kidney failure

Lead poisoning

Vitamin or iron deficiency

Newborn Testing for Sickle Cell Anemia and G6PD Deficiency

This test is mandatory as part of newborn screening programs. Most States also mandate screening for G6PD deficiency. These inherited types of hemolytic anemia can be detected with routine blood tests.

Diagnosing these conditions as early as possible is important for earliest treatment.

TREATMENT

 Treatments for hemolytic anemia include

·         Blood transfusions

·         medicines,

·         plasmapheresis

·         surgery,

·         blood and marrow stem cell transfusion and

·          lifestyle changes.

People who have mild hemolytic anemia may not need treatment, as long as the condition doesn't worsen.

People who have severe hemolytic anemia usually need ongoing treatment. Severe hemolytic anemia can be fatal if it's not properly treated.

Goals of Treatment

The goals of treating hemolytic anemia include:

Reducing or stopping the destruction of red blood cells

Increasing the red blood cell count to an acceptable level

Treating the underlying cause of the condition

Treatment will depend on

 the type,

cause,

and severity

Also to considered are age, overall health, and medical history.

In inherited form of hemolytic anemia, it's a lifelong condition that may require ongoing treatment.

an acquired form of hemolytic anemia,may be cured by treating the cause.

Blood Transfusions

Blood transfusions are used to treat severe or life-threatening hemolytic anemia.

.

DRUGS

Medicines can improve some types of hemolytic anemia, especially autoimmune hemolytic anemia (AIHA).

 Corticosteroids, such as prednisone, can stop  immune system from, or limit its ability to, make antibodies against red blood cells.

If there is no response to corticosteroids, other immunosuppressive drugs are used.

Examples include the medicines rituximab and cyclosporine.

For severe sickle cell anemia -hydroxyurea.

This medicine body to make fetal hemoglobin.

In sickle cell anemia, fetal hemoglobin helps prevent red blood cells from sickling and improves anemia.

Plasmapheresis

Plasmapheresis is a procedure that removes antibodies from the blood. For this procedure, blood is taken from the body using a needle inserted into a vein.

The plasma, which contains the antibodies, is separated from the rest of the blood. Then, plasma from a donor and the rest of the blood is put back in the  body.

This treatment may help if other treatments for immune hemolytic anemia don't work.

Surgery

Some people who have hemolytic anemia may need surgery to remove their spleens.

An enlarged or diseased spleen may remove more red blood cells than normal, causing anemia. Removing the spleen can stop or reduce high rates of red blood cell destruction.

Blood and Marrow Stem Cell Transplant

In thalssemia bone marrow doesn't make enough healthy red blood cells. The red blood cells it does make may be destroyed before their normal lifespan is over.

Blood and marrow stem cell transplants may be used to treat these types of hemolytic anemia.

A blood and marrow stem cell transplant replaces damaged stem cells with healthy ones from a donor.

During the transplant, which is like a blood transfusion, donated stem cells given intra -venously. Once the stem cells are in the body, they travel to bone marrow and begin making new blood cells.

Lifestyle Changes

If patient has AIHA with cold-reactive antibodies, patient must  try to avoid cold temperatures. This can help prevent the breakdown of red blood cells. It's very important to protect fingers, toes, and ears from the cold.

To protect himself ,  patient  can:

• Wear gloves or mittens when taking food out of the refrigerator or freezer.
• Wear a hat, scarf, and a coat with snug cuffs during cold weather.
• Turn down air conditioning or dress warmly while in air-conditioned spaces.
• Warm up the car before driving in cold weather.

People born with glucose-6-phosphate dehydrogenase (G6PD) deficiency can avoid substances that may trigger anemia. For example, avoid fava beans, naphthalene (a substance found in some moth balls), and certain medicines

How Can Hemolytic Anemia Be Prevented?

1.. Inherited types of hemolytic anemia cannot be prevented.

One exception is glucose-6-phosphate dehydrogenase (G6PD) deficiency.

2.If patient is  born with G6PD deficiency, he can avoid substances that may trigger the condition. For example, avoid fava beans, naphthalene (a substance found in some moth balls), and certain medicines

3.Some types of acquired hemolytic anemia can be prevented.

 Reactions to blood transfusion, which can cause hemolytic anemia, can be prevented. This requires careful matching of blood types between the blood donor and the recipient

.

4.Prompt and proper prenatal care can help one  avoid the problems of RH incompatibility..

 Rh incompatibility can lead to hemolytic anemia in a fetus or newborn.

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Key Points

• Hemolytic anemia is a condition in which red blood cells are destroyed and removed from the bloodstream before their normal lifespan is over.

• Hemolytic anemia is a type of anemia. The term "anemia" usually refers to a condition in which your body has a lower than normal number of red blood cells.

• Anemia has three main causes: blood loss, lack of red blood cell production, or high rates of red blood cell destruction. Hemolytic anemia is caused by high rates of red blood cell destruction.

• Hemolytic anemia can lead to many health problems, such as fatigue (tiredness), pain, arrhythmias(irregular heartbeats), an enlarged heart, and heart failure

• There are many types of hemolytic anemia. The condition can be inherited or acquired.

• With inherited hemolytic anemias, one or more of the genes that control red blood cell production are faulty. This causes your bone marrow to make abnormal red blood cells that die or are destroyed too quickly.

• With acquired hemolytic anemias, another disease or factor causes body to destroy red blood cells and remove them from the bloodstream.

• Hemolytic anemia can affect people of all ages and both sexes. Some types of the condition are more likely to occur in certain populations than in others.

• Signs and symptoms will depend on the type of hemolytic anemia and how severe it is. People who have mild hemolytic anemia often have no signs or symptoms. More severe hemolytic anemia may cause many signs and symptoms, and they may be serious.

• Signs and symptoms may include fatigue, shortness of breath, dizziness, headache, coldness in your hands and feet, pale skin, chest pain, jaundice (a yellowish color of the skin or whites of the eyes), pain in the upper abdomen, leg ulcers and pain, and a severe reaction to a blood transfusion

• Diagnosis of hemolytic anemia is based on medical and family histories, a physical exam, and test results.

• Treatment for hemolytic anemia depends on the type and severity of the condition. Treatments may include blood transfusions, medicines, plasmapheresis, surgery blood   and marrow stem cell transplantation, and lifestyle changes. People who have mild hemolytic anemia may not need treatment, as long as the condition doesn't worsen.

• usually can't prevent inherited types of hemolytic anemia, but you may be able to prevent some types of acquired hemolytic anemia.

• .Check regularly for ongoing care. Follow treatment plan and make lifestyle changes as recommended.

• If your child has hemolytic anemia, talk with his or her health care team about treatment, diet, and appropriate physical activities. 

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DEMENTIA-ETIOLOGY,CLINICAL FEATURES AND MANAGEMENT

                          DEMENTIA-ETIOLOGY,CLINICAL FEATURES AND MANAGEMENT

Dementia is acquired,global or multifocal involvement of cognitive functions causing decline in intellect,memory or personality in presence of normal conciousness.

    Causes of dementia

  1.Primary
  A. Alzimers disease-diffuse cortical atrophy
  B..Picks disease- frontal/temporal
  C.Frontal lobe degeneration

2.Secondary
Degenerative
                     Parkinsonism
                     Hereditary ataxia
                     Progressive supra nuclear palsy
                     Motor neuron disease
                     Huntingtons chorea
                     Multiple sclerosis

B.Conditions with raised ICT
                      Primary and secondary tumors
                      Hydrocephalus
                      chronic subdural hematoma
                      Carcinomatous meningitis

C.Vascular Dementia
                      Multi infarct dementia
                       Lacunar infarct
                       Thalamic infarct
                       diffuse atherosclerosis
                       Vasculitis-SLE, Polyarteritisnodosa ,Bechets

D.Chronic Infections
                       Syphilitic GPI
                       Tuberculosis
                        Fungal,protozoal
                        Slow virus disease(SSPE,CJ Disease,HIV

E.Dementia due to diffuse brain damage
                         Anoxia
                        Encephalitis
                        Acute head injury
                        Pugilistic dementia(in boxers)

F.Dementia due to endocrine disorders
                        Chronic hypoglycemia
                         Hypothyroidism
                         Hypo and Hyper parathyroidismAdrenal insuffiency
                         Cushings

G.Vitamin deficiency
                       B12,B1 deficiency and Niacin deficiency

H. Toxins
                       Alcohol
                       Drug and narcotic poisoning
                       Heavy metal intoxication
                       Dialysis dementia

I.Dementia in adolescents and young adults
                       Wilsons disese
                        progressive myoclonic epilepsy
                        Tuberous sclerosis
                        Leuko dystrophies
                        storage diseases
Common causes of dementia in the elderly 
                           Alzimers,vascular dementia,mixed dementia and Lewy body disease

Reversible causes of dementia in elderly
                         Metabolic,nutritional,Infections,psychiatric and drug inducedand autoimune .

TYPES OF DEMENTIA

I.Presenile sementia    Onset Before age of 65 Usually around age 40 or 50 .ExamplesPicks,Alzheimer

 II.Senile dementia      Onset after age65

III.cortical dementia    InPicks disease,Alzimers

IV.subcortica dementia -in Huntigtons disease,Multiple sclerosis

Differentiation between Alzimers and Picks disease

ALZIMERS	PICKS DISEASE
Diffuse involvement of the cortex	Focal involvement-frontal temporal
Pathologically neurofibrillary tangles,senile plaques	Picks bodies
Age of onset-presenile,senile	Presenile
Clinically features of diffuse cortical involvement	Fronto temporal features prominant

Clinical course:
rate of progression depends upon the under lying cause.
duration of symptoms helps to find the cause
alzimers disease is slowly progressive over the years
Encephalitis rapidly over weeks.
Cerebro vascular disease appear stroke by stroke

Factors accelerating dementia:
change of environment
inter current infection
Surgical procedures

Differential in initial phase;
Pseudo dementia of depressive illness.
History to be elicited
Rate of intellectual decline
Impairment of social function
general health and h/o stroke,head injury
drug history,family history
Nutritional status
Intellectual functions to be assessed
Memory
abstract thought
Judgement
Higher cortical functions
Neurological examination
Focal signs
primitive reflexes
pseudo bulbar signs
Involuntary movements
Neuro psychometric testing
Investigations:
CT brain
MRIscan
CSF pressure monitoring
Serumauto antibodies
tumor biopsy
CSF immunology
CSF viral antibodies
VDRL
TPHA
HIV status
serum B1
serum B12
serum folate
Metabolic and endocrine function test-
thyroid
para throid
renal
hepatic
adrenal
Treatable causes
nutritional,infective,metabolic and structural
Other cases
No effective treatment exists.
Many trials are in progress
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Pyrexia of Unknown Origin- Diagnostic Algorithm

   

                             Pyrexia of Unknown Origin- Diagnostic Algorithm   


             

ALGORITHM CONTINUED

ALGORITHM CONTINUED

ALGORITHM CONTINUED

ALGORITHM CONTINUED

ALGORITHM CONTINUED

ALGORITHM CONTINUED

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NOTE: 

CLINICAL EXAMINATION IS THE MOST IMPORTANT FIRST STEP  

According to the clinical condition,order of investigation can be changed.

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