Subacute combined Degeneration of the Spinal Cord

 

 Subacute Combined Degeneration of the Spinal Cord.

 P.K Ghatak, MD

This name Subacute Combined Degeneration of the Spinal Cord simply indicates how fast a disease develop and where the pathological changes happen in the spinal cord. The name does not give any hint of a cause or symptom it produces.

Subacute Combined Degeneration of the Spinal Cord (SCD of the SC) is a slowly developing disease due to degeneration of the myelin of the spinal cord. The spinal cord, like a cable line, containing several bundles, each bundle carries electrical signals either to or from the brain. Each bundle carries a separate set of information. A cross-section of the spinal cord at the neck level is shown here.

In SCD the Dorsal and Lateral columns of the upper thoracic and lower cervical part of the spinal cord are affected and in late cases the descending fibers of the motor cortex, the Corticospinal tact, of the upper cervical region is damaged.

The dorsal column carries fine touch, vibratory sensation, conscious sensation of position of the body (proprioception), two point discrimination from the skin and joints to the sensory area of the brain.

The lateral column carries pain and temperature sensation from the skin to the brain.

The corticospinal tract carry voluntary motor impulses from the brain to the lower motor neurons located in the Ventral Horn of the spinal cord.

The cause of SCD of the SP:

It is due to deficiency of vitamin B12.

Vitamin B12 is a cofactor of two important enzymes, (a) Methionine synthase and (b) Methymelonyl CoA mutase.

Methionine synthase is required for methionine synthesis, a crucial amino acid required for myelin synthesis.

Methymelonyl CoA mutase is required for fatty acid synthesis, an important ingredient for myelin. This enzyme is also important for synthesis of Thymidine which goes to from DNA in humans, Macrocytic anemia develop due to deficiency of this enzyme.

In absence of B12 the myelin breaks down and not repaired due to deficit of two critical components of myelin and as a result the symptoms of SCD of SC develop.

Blood levels of vitamin B12 do not correspond with the tissue levels, which show deficit much earlier than B12 levels of the blood due to the fact that most B12 in the blood are combined with protein.

Symptoms of SCD:

The initial symptoms are tingling and numbness of the legs, symmetrical is distribution on each sides of the body and the deficit areas gradually extends upwards. This is followed by loss of position sensation, difficulty in coordination and ambulation. Later, loss of temperature sensation of the lower and upper extremities results in thermal burns. As the disease further advances, clumsiness of movements, and muscle weakness, spasticity of limbs and paraplegia develop due to corticospinal tract involvement.

Causes of B12 deficiency:

Vitamin B12 is a water soluble vitamin. Animal protein, eggs, fish, shell fish and milk are the only source. Highest concentration is seen in abalone and animal liver. Plants are no vitamin. In the USA, the cereals are fortified with B12.

Vitamin B12 deficiency develops for the following reasons.

1. Diet.

2.  Parietal cell disease of stomach.

3. Disease of the terminal ileum. 

4. Congenital.

5.   Medications

Diet.

The vegans in the USA are at risk of developing B12 deficiency, pregnancy and breastfeeding are risk factors.

Parietal cells.

Chronic gastritis destroy the parietal cells of the stomach. The intrinsic factor is a glycoprotein. It combines with vitamin B12 released from the food, and the composite is protected from further digestion and is carried to the terminal ileum for absorption. Partial gastrectomy, Roux-en-Y operation, bariatric surgery etc. removes the parietal cell population and B12 deficiency occurs.

Autoimmune disease.

Antibodies produced in the body to fight pathogen, but in this case the antibodies mistakenly think that parietal cells as foreign and attack and destroy them, in other cases the antibodies attack the intrinsic factor itself and eliminate from the body. The final outcome is vitaimB12 absorption stops. Three diseases results from vitamin B12 deficiency.  One is pernicious anemia, two-  peripheral neuropathy and three - SCD of the SC.

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Diseases of ileum.

Crohn's disease, malabsorption syndrome, short loop syndrome, ulcerative colitis, sprue, lymphoma of abdomen and amyloidosis are some of the diseases producing B12 deficiency.

Fish tape worm – A parasitic tape worm, Dibothriocephalus latus, steals vitamin B12. Humans acquire this parasite by eating raw fish. Until now, this fish tape worm infestation was confined to the Far East but popularity of sushi food in the West putting more people at risk.

Congenial. This is rare finding, due to gene mutation parietal cells do not produce intrinsic factor at all or produces only in small quantity.

Medication. Acid production in the stomach can be stopped by Pantoprazole and to a lesser degree by H2 (histamine receptor 2) blockers. Acid in the stomach is necessary for releasing vitamin B12 from the food substances in the stomach.

History of Pernicious anemia and Vitamin B12.

Before the organic chemistry entered the medical fields, a careful physical examination and autopsy findings were the only tools known to physicians for determining a cause of an illness. In1799 and 1800s in Scotland and Scandinavian countries, the elderly, particularly the women, were suffering from a slowly progressing fatal disease due to anemia. It was rightly named Pernicious anemia. In 1812 Dr. Comb reported finding atrophic gastritis of a man died of anemia. Subsequently, between 1945 and 1926, Drs. Addison, Blamer, Whipple and Minot and Murphy published papers linking pernicious anemia with vitamin B12 deficiency.  In 1934 Drs. Minot, Murphy and Whipple received the Nobel Prize in medicine for their discovery.

Autopsy finding in Subacute Combined Degeneration of the Spinal cord.

Multifocal spongy vacuolated lesions of the dorsal, lateral and corticospinal tracts in the thoracic and cervical sections of the spinal cord, associated perivascular infiltration with foamy macrophages and lymphocyte, and interstitial edema are distinct pathological changes of myelin degeneration.

Diagnosis of SCD.

A good history followed by neurological examination are all that needed for making an initial diagnosis which is supplemented by the presence of vitamin B12 deficiency in the nervous tissue, and associated with a typical macrocytic anemia and peripheral neuropathy.

Confirmation of vitamin B12 deficiency.

Blood level of vitamin B12 may or may not be low but serum homocysteine and methylmelonic acid will be high because conversion of homocysteine to methylmelonic acid and then to S-adenylyl methionine are completed by by vitamin B12, acting as a cofactor; in its absence of B12, both homocysteine and methylmelonic acid accumulates in the blood. Blood level of homocysteine is over15 mcmol/L and methylmelonic acid is >260nmol/L.

Macrocytic anemia.

The red cells are large and oval in shape and the MCV (mean corpuscular volume) volume in macrocytic anemia is on the average over 115fL [f=10 to the power of -15] and each red cell have a central pallor. Mild leukopenia and thrombocytopenia also accompany a high MCV. The neutrophils have 6 or more lobed nuclei.

Serum LDH (lactic dehydrogenase enzyme) and unconjugated bilirubin are higher due to high turnover of the red cell precursors in the bone marrow.

In most cases, MRI of the spine is not essential. In case of any doubts, a bone marrow examination can clinch the diagnosis.

The next step is to identify the etiology of a given case. That involved various tests specific for that case only.

Treatment.

Replacement of vitamin B12 is the key, and the earlier it is done, the earlier recovery is achieved. Various protocols are available, but a standard one is 1000 mg of vitamin B12 is given subcutaneously each week for 6 weeks then once a month for 12 months. If the primary reason for B12 deficiency is not amenable to treatment, then B12 monthly injection is continued for life long. Otherwise, oral B12 therapy may be possible. 

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Hodgkin Lymphoma

 

 Hodgkin Lymphoma

P.K.Ghatak, MD

Thomas Hodgkin, a British physician and pathologist, published a paper in1832 describing the autopsy findings of 7 patients with with painless enlarged lymph nodes associated with enlarged spleen. In subsequent studies more such cases were described by others and in 1912 the decease was named as Hodgkin Lymphoma. Dorothy Reed Mendenhall of U.K. and Carl Sternberg of Germany published in 1902 their histological studies of Hodgkin's lymphoma. They detected large cells with binucleated nucleus due to non-separation of cytoplasm after the cell division. Sternberg mistook the cause of this illness due to tuberculosis, but Dorothy Reed showed these cells had no relation with Mycobacterium tuberculosis. Now, these multinucleated cells are called Reed-Sternberg cells. These cells are formed in the germ center of B- type progenitor lymphocyte due to the mutation of genes, perhaps due to prior infection of Epstein Barr virus. Numerous leukocytes and immune cells gather around the Reed-Sternberg cells, producing engagement of the lymph nodes and spleen. The Reed-Sternberg cells are malignant. The cells express C 15 and CD30. Lacunar type of Reed-Sternberg cells are mono or binucleated cells with a small nucleolus and has a large pale cytoplasm, the Classic type of Reed-Sternberg cells are large, have binucleated nuclei with multiple eosinophilic nucleoli and clear cytoplasm.

Hodgkin lymphoma and lymphocytic leukemia both are malignant transformation of lymphocytes. But they are different diseases. Malignancy of B-type of lymphocytes produces Hodgkin lymphoma. The malignant cells adhere together and remain within the lymph nodes, and no malignant cells appear in the peripheral blood. In lymphatic leukemia, both B-lymphocytes and T- lymphocytes of the bone marrow turn malignant and cancer cells are present in the peripheral blood and dominate among the other blood cells. Mutation of DNA are responsible for both cases but the exact cause in unknown why in one instant it becomes a lymphoma in other a leukemia. The chronic form of lymphocytic leukemia is an indolent disease and requires no treatment unless patients develop anemia or the immature lymphocytes called Lymphoblasts are seen in numbers more than 20 % of the lymphocytes (acute lymphoblastic leukemia).

Hodgkin lymphoma is closely related to another malignancy of lymph nodes called Non-Hodgkin lymphoma. The main points of difference between them are summarized in this table.

Points of difference

	Hodgkin lymphoma	Non-Hodgkin Lymphoma
Lymphocyte type	B-cell	T- cells and B-cells
Reed-Sternberg cell	Present	Absent
Location of Glands	Neck and above the diaphragm in chest	Any lymph nodes, both above and below the diaphragm
Age of patients	Young	Generally 65 yrs and over
Sex of patients	Generally male	Both sexes
Race	White	Asian and African
Response to treatment	Good	Poor
Prognosis	Good	Not good

Symptoms of Hodgkin lymphoma.

General Symptoms: Like all malignancy, unintended weight loss, poor appetite, nausea, and weakness also develop in Hodgkin lymphoma.

Specific symptoms: Though no one symptom can identify Hodgkin lymphoma, but these symptoms are suggestive of this disease. Painless cervical lymph nodes enlargement which persists. Profuse night sweats. Breathing difficulty due to pressure on airways in the lungs. Itching which intensify after bathing or drinking alcohol. Fever of unknown origin, skin rashes and neuropathy.

Investigation.

Diagnosis of Hodgkin lymphoma depends on finding Reed-Sternberg Cells in the biopsy of a lymph node or bone marrow. Other tests are performed to find the disease stage and other organ involvement.

Cellular types and classification of Hodgkin lymphoma (HL).

The WHO classify Hodgkin lymphoma, based on histological and clinical features into 5 types of Hodgkin lymphoma.

1. Nodular Sclerosis. This type HL is most common. The bands of fibrous tissue divide the mass into several nodular areas. R-S cells are Lacunar type. The nodes are detected in the mediastinum and supra diaphragmatic locations. Patients are generally teens and young adults

2. Mixed cellular. This type is the next common HL. The R-S cells are classical R-S cells. Patients are generally HIV positive, disease stage is advanced and enlarged nodes are found in the abdomen in addition to usual places. Patients are generally older around 65 years.

3. Lymphocyte depleted. This is a rare type of HL. R-S cells are abundant, these cells express Eptein virus antigens. Leukocytes and immunocytes are few.

4. Lymphocyte rich. This type is also rare. R-S cells are lacunar and classical types. Profuse Infiltration by other cells, among them lymphocytes predominate.

5. Nodular lymphocyte dominant. R-S cells are infrequently present, dominant cells are normal lymphocytes and histiocytes. The lymphocyte expressing CD 20 but not CD15 or CD39.

Staging: Like any other cancers, HL are classified accordingly using well established criteria into 4 classes and treatment are prescribed accordingly.

Several modalities of treatment are available, as follows.

1. Combination chemotherapy

2. Radiation therapy

3. Immunotherapy including Check point inhibitors, CART therapy. Monoclonal antibodies and Small molecules.

4. Bone marrow and Stem cell transplantation.

Stage I and II.

Combination of chemotherapy agents are given is 2 cycles, each one of 4 weeks duration. This is followed by radiation therapy. Prognosis is very favorable. Those who has additional risk factors like immunosuppression are given 4 cycles of chemotherapy and in increased dosage.

Stage III and IV.

Combination chemotherapy with additional agents are given in 6 cycles, followed by radiation and Immunotherapy. Prognosis is poor to unfavorable.

Separate protocols are available for recurrence of the disease and poor initial response to the therapy.

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Peripheral Neuropathy

 

Peripheral Neuropathy

P.K. Ghatak, MD.

The part of the nervous system that lies outside the Brain and Spinal Cord is known as the Peripheral Nervous System. It consists of both somatic and autonomic divisions; and each division consists of sensory and motor nerves. There are two sets of peripheral nerves. One, those arise from the brain called Cranial Nerves- 12 pairs in number and two, those arise from the spinal cord called Spinal nerves- 31 pairs in number. All the spinal nerves are mixed nerves, made up of both sensory and motor fibers; whereas the cranial nerves can be pure motor, sensory or mixed containing both motor and somatic sensory and special senses. These are smell, vision, hearing and position of the head in space and taste sensations.

This anatomical characteristics require a through basic knowledge of the nervous system in order to fully comprehend the clinical spectrum of the peripheral neuropathy.

This diagram below illustrate the anatomy of a spinal nerve formation, and shows sympathetic fibers been carried by a spinal nerve.

                                             

                                                           Copied from a NIH publication.

Symptoms of Peripheral Neuropathy.

Development and progression of of symptoms of peripheral neuropathy are depended on the cause.

Using diabetic neuropathy as an example, because it is the most common cause of Peripheral Neuropathy. 

The symptom begins with numbness and loss of light touch sensation in the feet and progress upwards in the legs and thighs. It is a slow but progressive and generally bilateral and often symmetrical in distribution. Gradually the pain, pressure, vibration and temperature sensations are lost. Patients frequent fall to the ground because of lack of sensation and develop progressive osteoarthritis of knees and ankles, due to absence of pain from these joints. Similar changes also happen in fingers and hands. Frequently things fall off the hand and burning of fingers are common occurrence. Others develop burning pain, which is felt more intensely at night in bed.

Loss of motor function of eyes results in double vision, difficulties in reading and writing. Wasting of muscles and loss of muscle mass, easy fallibility and generalized weakness follow. Autonomic functions abnormality manifests as decreased or absence of secretion from all glands, lack of sweating, hypotension, lightheartedness, dry mouth and eyes, difficulty in urination, impotency in male and constipation.

Causes of Peripheral Neuropathy:

Beside diabetes mellitus the following are important causes:- Chronic alcoholism, Vitamin B1, B6, and B12 deficiency, Malignancy, Infection and Reactivation of dormant pathogen, direct injury to the nerves in accidents and burns, Systemic illnesses, Pressure on nerves by abnormal metabolite, Autoimmune diseases, Congenital, Poisoning, Side effects of prescribed medication, and idiopathic.

Chronic alcoholism. Malnutrition and vitamin deficiencies are components of alcoholism. Nerve fibers require a healthy myelin sheath in order to propagate nerve impulses; the myelin sheath is damaged by alcohol. Eventually, permanent damages occur in the nerve fibrils. Initial symptoms are double vision due to lateral rectus muscle paralysis of the eyes and difficulty in focusing for reading. Pain in arms and legs and numbness are next common symptoms.

Vitamin B Deficiency. Vitamins B1, B6 and B12 are commonly referred to as nerve vitamins. RBC B12 level corresponds with nerve tissue B12 level, which is more accurate than the serum B12 level. Numbness and pins and needles are common symptoms and generally isolated nerves of one legs are common and if both legs are the affected the areas are not symmetrical. Severe vitamin B1 deficiency is well known as Beriberi.

Infection of the peripheral nerves. The recent COID-19 epidemic, and HIV/AIDS in the preceding years, recorded high incidence of neuritis developed in various areas of the body. Lyme disease is another common case of direct nerve infection. Leprosy is still a leading case of disabling and deforming disease due to direct invasion of peripheral nerves by Mycobacteria leprae in the South Asian countries. Reactivation of dormant chicken pox virus produces Shingles. It is an extremely painful vesicular eruption of the skin, Serious eye problems result when the 5^th Cranial nerve is infected, ophthalmic branch lesions can produce blisters of the involved skin dermatome and cornea blisters can produce blindness.

Systemic diseases. Systemic disease is a process where every organ and tissues are venerable to the same pathological changes. Vasculitis is the worst disease from this aspect. Many peripheral nerves develop vasculitis at various locations, one at a time or several simultaneously. Both sensory and motor nerves are commonly involved. Nerve fibers derive nutrition from tiny arterial branches from muscular arteries, and vasculitis cuts arterial supply to the nerve fibers.

Collagen vascular diseases like Lupus, Sjorgen syndrome and occasionally Rheumatoid arthritis are examples of neuropathy due to several pathological processes affecting peripheral nerves.

Other systemic diseases, for example Whipple disease of the intestine, prevents fat soluble vitamins A, D, E and K absorption from the small intestine. These vitamins are required for maintenance of Myelin sheath of the nerves, deficiency of these vitamins causes neuropathy.

Malignancy. Cancers of solid organs, Myeloma, Leukemia and Lymphoma produce peripheral neuropathy. In adults developing neuropathy for the first time, otherwise in good health, the malignancy becomes an important issue and must be excluded without further delays. Cancer cells generally infiltrate adjoining tissues and the nerve fibers that are content in it. Relentless pain is the main symptom. Myeloma produces abnormal proteins in large amounts. These protein molecules are deposited in and around the nerve-vascular bundles and produces neuropathy. With the growth of myeloma, the bone marrow is over stretch and erosion of bone at the growing site produces deep-seated nagging pain over the spinal column in addition to distant neuropathy. Certain cancers secrete polypeptides which can interfere with neurotransmitters and produce numbness and pain.

Lymphomas are bulky tumors, they put pressure on the nearby nerves. Lymphoma can also produce antibodies which can mistakenly attack nerve tissue, causing an autoimmune disease.

Carpal tunnel syndrome. The median nerve at the front of the wrist has to negotiate through a tight bony passage between small wrists bones and any extra materials like amyloid, inflammatory cells in Sarcoidosis or mucoproteins in Hypothyroidism usually accumulate in and around the median nerve and produced pain and weakness of fingers and thumb and claw hands develop in late cases. Carpal tunnel syndrome may be unilateral or bilateral.

Congenital. Acute Intermittent Porphyria is an autosomal dominant inherited disorder due to the absence of one or many of the 8 enzymes required for Heme synthesis. Heme is a part of Hemoglobin. This results in accumulation of intermediate metabolites, chief among them is delta Aminolevulonic acid. Intermittent attacks consist of – (a) paralysis of limbs and muscles of respiration, and acute pain and (b) eruption of blisters on sun-exposed skin, and various GI symptoms including abdominal pain and (c) Hallucination, seizures and psychosis. Attacks are precipitated by certain medications and food or starvation. An attack usually lasts 7 to10 days, but attacks are recurrent.

Poisoning. Lead and Mercury are poison to humans, specially if it happens in a growing child. Lead pipes and paints are the primary source of lead poisoning. Shrimp farming and bottom feeders fish cultures are the chief source of mercury poisoning. FDA has successfully limited other sources of mercury poisoning by regulating its use in industries and laboratories. In lead poisoning, the paralysis of motor nerve fibers of the extensors of the wrist and ankles are primarily affected, resulting in wrist drop and foot drop. Motor skill in the developing child is markedly limited.

Mercury binds with sulfhydryl group on proteins and paralyses enzymes and disrupts calcium movements in the neurons and myelin sheaths. Disruption of normal function produces neuropathy. The main features of mercury poisoning are tremors of finger, eyelids and lips, numbness of hand and feet, incoordination of movements and ambulatory difficulties and memory.

Autoimmune inflammatory neuropathy. Guillain-Barré syndrome is an autoimmune disease, acquired in most cases after a viral infection, but other infection like Mycoplasma can produce this acute life-threatening illness. An acute inflammatory demyelinating polyradiculopathy and causes paralysis of lower part of the body then rapidly progress upwards and paralyses the Diaphragm and other respiratory muscles. In some others, the paralysis stars in the eye muscles and muscles of the eyelids and lips, then spreads.

Peripheral neuropathy in adults must be investigated thoroughly, specially in an otherwise healthy individual, due to possible presence of a developing malignancy. Just making a diagnosis of neuropathy is too simplistic and inadequate without finding the etiological cause in that individual.

Footnotes:- many diseases very briefly mentioned here, one may read more about them by finding previous blogs in humiheath.blogspot.com

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Septicemia and Sepsis

 

Septicemia and Sepsis:

P.K. Ghatak, MD

These two terms are often used interchangeably but they do not covey the same meaning. Septicemia means tissue damages from blood-borne pathogens – primarily bacteria or viruses. Sepsis indicates tissue damages from released of Cytokines, TNF and inflammatory Interleukins from the accumulated blood cells and immunocytes at the site of infection.

Septicemia:

Whenever a harmful agent gets inside the body, the body tries to put a barrier around it so that the harmful agent does not spread to other parts of the body. But due to a number of reasons, this may fail. And if the agent a biological agent, it invades tissues widely and enter the blood stream. The presence of live biological pathogen and damage produce by its toxins is called septicemia.

Our body is pre-programmed to repose by a set pattern of actions called 1. Innate or inherited immune reaction. 2. And by a separate set of actions, from experience gained from encounters with the offending agents, called Acquired Immune reaction.

1 Innate reaction :

The skin, surface layer of the nose, mouth, GI, Respiratory and Genitourinary tracts are the physical barriers to invaders. Once that defense is breached, then the responsibilities fall on the surveillance cells for finding the invaders by the immune cells called Dendritic cells. Dendritic cells recognize the molecular patterns of the invaders' surface membrane, and the dendritic cells attach themselves to it, like a key fits a lock. Then, these immune cells release chemicals, called Cytokines. In repose to cytokines, neutrophils, monocytes, eosinophils, phagocytes and complements (present in plasma) gather at the site. And a series of actions and reactions take place in the local area resulting in increased blood flow, redness, swelling, temperature elevation and temporary loss of function.

This is called, Classical Pathway. Other paths are - Alternate Pathway and Mannose-Lectin Pathway. These pathways are activated when the invaders are yeasts, viruses and certain other groups of bacteria.

The end result of all pathways are that the same. The invasion is checked, the invaders are paralyzed and eaten alive by the macrophages, and the dead bodies are removed from the area in order for healing to take place.

Adaptive Immune Reaction:

Acquisition of adaptive immunity is a learned process. During the first encounter with a pathogen, a signature part of the pathogen - usually, a protein molecule called antigen is recognized by the dendritic cells and the information is passed in succession to lymphocytes of various designations like B-cells, T-cells and ultimately to antibody producing B-lymphocytes. B-cells produce immunoglobulin, specific for that antigen, which when combines with that antigen of the invader, it neutralizes the pathogen. This antigen remains in memory in a subset of B -cells called Memory cells. These lymphocytes live in the regional lymph nodes and the duration of memory is temporary, whereas those B-memory cells move to the bone marrow retain memory permanently.

Like innate immunity, adaptive immunity also consists of a cellular component and a Humoral component.

One can well appreciate there are plenty of opportunities for the invading pathogens to neutralize or evade this body's defense system due to systemic illness or congenital immune deficiencies or use of immune modifying medications or any combination of these. These conditions favor onset of septicemia.

Sepsis:

Sepsis is a severe clinical condition and carries a mortality over 50 %. The inflammatory reactions mentioned in Septicemia are operative here also but in aggressive and unregulated manner in sepsis. During COVID-19 endemic, the high death rate was due to this process and Cytokine Storm term was used to describe this phenomenon. In sepsis, failure of the heart, lungs, kidneys, brain and liver occurs together. A paper published on sepsis based on worldwide case studies, showed Gram negative infection accounted over 50% of sepsis, and gram positive bacteria, fungi and viruses accounted for the rest. The source of infection in order of frequency were the lungs, abdomen, and urinary tract and the underlying conditions that favors sepsis were diabetes mellitus, congestive heart failure, renal failure.

Mechanism.

Most harmful pathogens carry potent endo and exotoxins. These toxins act in many ways to kill or paralyze immune cells and cause tissue injury. Adhesion of endothelial lying cells are weakened and pathogen and toxins gain entry in the organs and continues to damage tissue. White blood cells in their cytoplasm have powerful enzymes in packets called granules and released enzymes are primarily directed towards the pathogens but when produced in excess amount it kills normal cells also and contribution organ damage. In addition, in sepsis major alteration in the concentration of blood coagulation factors takes place due to its effect on liver and local tissue. This causes hemorrhage and also decimated intravascular coagulation and rapid organ failure.

Effect of sepsis.

Vascular wall damage and derailed maintenance of vascular tones and depressed cardiac output produces hypotension and change in consciousness or unconsciousness. Blood flow through the lung capillaries diminishes markedly, producing hypoxia, generation of oxygen radicals and superoxides and more tissue necrosis. Similar changes in the kidneys produce renal failure and electrolyte imbalance.

Role of Macrophages in Sepsis.

Macrophages are of 3 types - resident tissue macrophages (RTMs), monocyte-derived macrophages (MDMs), and transitioning MDMs in the tissue.

Macrophages express a number of proinflammatory chemokines and cytokines, including IL-1β, IL-6, IL-8, CXCL10, and TNFα. And a macrophage subset termed Macro_c2-CCL3L1, which specifically expressed CCL8, CXCL10/11, and IL-6, and a monocyte subset termed Mono-c1-CD14-CCL3, which abundantly expressed IL-1β, CCL20, CXCL2, CXCL3, CCL3, CCL4, and TNF alpha.

Macrophage hyperactivation.

Hyperstimulated macrophages produce Hemophagocytic lymphohistiocytosis (HLH) and macrophage activation syndrome. Hemophagocytosis (i.e., engulfment of erythrocytes by activated macrophages), systemic inflammation, fever, cytopenia, hyperferritinemia, and hyperlipidemia, which can be due to inherited defects in cytotoxic T-cell function or triggered secondary to infection or rheumatological disorders.

Role of Platelets in Sepsis. Platelets are tiny lens like discs and platelets have no nucleus but the cytoplasm is packed with powerful chemicals in packet from. Though platelets lack in size but make that up in numbers, around 200,000/microlit of blood. In inflammation and specially in Sepsis, cytokines induce rapid release of platelets from the bone marrow and make individual platelet swell and the surface becomes more sticky and adhere to each other into tiny clots and blocks blood flow in capillaries. This leads to ischemia and tissue necrosis of the kidneys, liver, brain and lungs. Arterial blood fails to load up oxygen and all highly vascular tissues fail to function normally and contribute to necrosis. Released chemicals from platelets recruit further inflammatory cells at the site.

Cytokines in Sepsis.

LTB4. Promotes the release of inflammatory cytokines, recruits neutrophils, increases neutrophil chemotaxis, causes degranulation of neutrophils, increases interaction between neutrophils and endothelial cells, stimulates the release of mediators, enzymes and superoxide, increases ( Interleukin) IL 6, increases pain perception by lowering pain receptors threshold.

ILs are stimulators of inflammation.

These ILs are IL-1, IL-6, IL-12, IL-18 and IL-23

The most pro-inflammatory Cytokines are IL-1 beta and TNF alpha.

Pro-inflammatory ILs activate CD2, CD4, CD8, CD27, CD134 and CD137.

Inhibitors of inflammation ILs are-

IL-10, IL-6, IL-1 beta. They activate CD80, CD152, CD160, and CD223.

Interleukins are secreted primarily by immunocytes. Interleukins (ILs) are hormones like chemicals, function as an inflammatory promoter but also act as anti-inflammatory agents. In the biological system, pro and anti, inflammatory agents are neither good nor bad. Both are required to fight infections, autoimmune diseases and cancers and at the same time must be available for repairs of diseased or damaged tissues. Interleukin 6 (IL-6) is the main Interleukin in the pathogenesis of COID-19 virus inflammatory reactions. 1. IL-6 promotes inflammation. 2. Anti-inflammation. 3. Pathogen clearance. 4. New blood cell formation (hemopoiesis) 5. Reset the metabolic rate of the body. 6. Modification of lipid metabolism. 7. Neural differentiation increased substance-P generation and myelin sheath break-up.

Prostaglandins in Sepsis.

Prostaglandins are produced by a number of cells, some are immunocytes others are not immunocytes. It is derived from Arachidonic acid. PGI2 is a potent vasodilator, and an inhibitor of platelet aggregation, leukocyte adhesion, and prevents smooth vascular muscle proliferation. PGI2 receptors are expressed in the kidney, liver, lung, platelets, heart, and aorta. PGD2 is synthesized in both the central nervous system (CNS) and peripheral tissues. In the brain, PGD2 regulates sleep and pain perception.

Syndrome in Clinical Medicine

Syndrome in Clinical Medicine

P.K.Ghatak,MD

In a NIH publication in 2003, Dr. Franz Calvo et al, defined syndrome as a recognizable complex of symptoms and physical findings for which a direct cause is not necessarily understood. Once the medical science identifies a causative agent or process with a high degree of certainty, physicians may then refer the process as a disease and not a syndrome.

Some well known syndromes now are called diseases and to illustrate - an example is Cushing's disease and Cushing's syndrome. In 1912 Dr. Cushing reported a new disease he call polyglandular syndrome due to malfunction of the Anterior Pituitary gland, He published this entity in 1932 as basophil adenomas of the Pituitary body and named it Pituitary basophilism. Symptoms of the disease - gained excessive weight, mostly around the back of the neck, face and abdomen. Also developed high blood pressure, diabetes, acne and facial hair. In subsequent years the condition was known as Cushing's syndrome. Further studies identified the cause was a tumor of anterior pituitary producing an excess amount of ACTH hormone which in turns putting out excess corticosteroids from the Suprarenal glands. Similar changes were also detected when patients took steroid for a prolong time, as one of the anti-rejection drug following kidney transplants. And also seen in certain cancer of lungs secreting excess amount of polypeptide having similar hormone like actions of the suprarenal gland. Now Cushing's Disease term is reserved for symptom complex arising from tumor of the anterior pituitary and Cushing's syndrome is applied all others causes which can produce some features of Cushing's disease.

If one looks up Syndrome in the Wikipedia, will be surprised to find more than 1600 syndromes. In the index of any textbook of medicine where every entry is listed in alphabetical order, one finds only 3 entries under syndrome, the rest of the syndromes are under the first letter of a name attached to the person discovered the illness. Not all the listed syndromes, however, follows this rule. Some names are retained because the name refers to well understood symptoms by the public, like - Milk - Alkali syndrome and Irritable Bowel Syndrome.

Recent rapid advances in genetics, MRI imaging , sonography, immunology and biochemist solved many obscure causes of syndrome. In the lifetime experience of any well rounded physician might have not see more than 30 syndromes. Certain specialties like Pediatrics are likely see more syndromes.

A few syndrome will be presented, one or two from each group,  to give a chance to the readers the mistery about syndrome.

Down syndrome.

Down syndrome arises from abnormalities of chromosome 21. It occurs in 75% cases as inherited and 25% as spontaneous. Each cell of the body contain an additional one full or partial copy of chromosome 21. This generally happen as non-jurisdiction or translocation between chromosome 21 and 14 or 21 and 21 or 21and 22. In 2 to 3 % cases it also occur due to Mosaicism.

Some of the common features of Down syndromes are mental retardation, flat cranium and flat nose bridge, a short neck, large tongue compared with the floor of the mouth, prominent epicanthal fold, structural heart defects, truncal obesity, poor muscle tone an delayed mile stones of development.

Polycystic Ovary Syndrome.

Originally the Polycystic Ovary syndrome was called Stein-Leventhal syndrome because this pair of investigators were the first to report it in 1935. In 1990 NIH added two additional criteria - multifactorial genetic errors and insulin resistance, and finally in 2003 ultsonographic detection of more than 20 cysts in ovary was added and named it Polycystic ovary syndrome. The cause of this syndrome is unknown and symptoms vary widely.

A typical case have these features: Symptoms of irregular and scant menstrual flow or delayed monarchic. Development of acne and facial and body hair of masculine type, obesity, hypertension and insulin resistance and diabetes mellitus. Most cases are due to excessive androgen activities but androgen is normal in minority of cases. In few cases the polycystic ovary syndrome is detected during investigation of failure to conceive. If not treated properly there is high likelihood of development endometrial carcinoma later in life.

Klinefelters syndrome. This congenital condition affects only male child due to having an extra X chromosome. The condition is also known as 47 XXX. The genetic abnormality occur randomly either in the development of ovum or sperm. The condition is generally detected at puberty when the child failed to develop muscle mass and develop feminine body type - gynecomastica, no facial hair and wide hips. They have small genitalia and testicle, scant or absent sperm production and have long legs and short torso. Many have learning difficulties and lags behind reading and writing skill.

Not all affected have all the above features and may pass as normal and only correctly diagnosed much later when one fails to father children. They carry risk of breast and extragonadal germ cell cancers and also osteoporosis.

Turner's syndrome. Turners syndrome is also known as 46 XO. This congenital condition is seen only in female offspring, arises due to missing a whole or part of sex chromosome X; but whether that missing X chromosome is paternal or maternal is not known. The gene responsible for bone growth is SHOX gene and it is missing in Turners syndrome results in the abnormalities of bones in Turners syndrome. At birth the child may appear normal except for a web neck and a broad chest. As the child reaches age 9 or 10 the growth slows down, develop no secondary sexual characters and menstrual cycles. Other features are cubits vulgus, aortic/ pulmonary stenosis and high BP, diabetes mellitus, hypothyroidism and osteoporosis.

Fragil X syndrome: It is a X link cause of mental retardation. Males are more severely affected than females. Incidence is 1:4000 male birth and 1:10,000 in females. Symptoms in female are learning difficulties, variable degrees mental retardation and early onset of menopause. In male the physical characteristics are large ears, prominent jaw bone, high pitched voice, Mitral valve prolapse and increased immobility of joints. This syndrome is associated with autism.

The tip of the long arm of chromosome X carry the mutated Fragil RNA gene results from undue expansion of CCG repeats. More repeats are present more mental retardation is detected.

Marfan syndrome. Marfan syndrome is an autosomal dominant inherited disorder of the connective tissue due to mutations in the Fibrillin gene (FBNA1) on chromosome 15. This results in aberrant TGFB1 and TGFB2 activities. Clinical features of Marfan syndrome are tall structure, long arms and legs, scoliosis, pigeon chest wall deformity(Pectus excavatum), dislocated eye lenses, mitral valve prolapse, aortic root dilatation, aortic incompetence and aortic aneurysm and dissection.

Ehlers-Danlos syndrome. This is another connective tissue autosomal dominant inherited disorder. Mutation of many genes, last count 20 genes, are implicated, and based on severity of symptoms 11 varieties are known. Those who have severe symptoms have mutation of COL5A1 and COL5A2 genes, other mutated genes are TNXB, ADMTS2, PLOD1, FKBP14 and many others. Mutations result is formation of collage tissue in a haphazard fashion and functionally of poor quality specially of the skin, skeletal muscles, arteries, bones and internal organs. Major symptoms include fragile velvety skin, which peals off easily and forms extensive scars. Aneurysm of artery and dissection and rupture of aneurysm and other changes of eyes, heart and bones mentioned under Marfan syndrome.

Irritable bowel syndrome. Irritable bowel syndrome fits the classical definition of the syndrome. A group of symptoms originate in colon and small intestine but cause remains known. Common symptoms are - a sense of not able to evacuate completely after a bowel movement, constipation and low grade abdominal cramps, flatulence and diarrhea, often hard and lumpy stool and diarrhea on the same day, and several bowel movements a day. Various theory are put forward including stress, pressure of modern life, precooked meals, food additive, change of colon bacterial colonies and low tolerance to pain. Both sexes are affected and age of onset - from teens to elderly. It is a common illness.

Milk-Alkali syndrome. It is a self made syndrome due to taking an excessive amount of Calcium supplement to prevent osteoporosis and condition is accelerated and made worse taking mega dose vitamin D3. In previous generation people suffered this complication from taking excessive amount of Tums, Maalox and Mylanta for heart burns and peptic ulcer diseases. Excess alkali present in the form of carbonate in these compounds shifts the blood pH towards the alkaline side. High blood calcium results in excess amount of calcium excreted in the urine. Kidney stones and urinary bladder stones may develop. Renal colic, chronic pain around loin and back are usual symptoms of kidney stone. Left untreated, patients may end in renal failure.

Abdominal Compartment syndrome. This is a serious and often fatal condition arises from several causes but often seen in severe burn victims. Other causes are organ transplants, prolonged abdominal surgery specially repair of abdominal aorta rupture, bullet or knife penetrating injury with severe intra abdominal hemorrhage. Sepsis, abdominal abscess, severe peritonitis and others. Fluids and inflammatory exudates accumulate in and around organs and raises intra abdominal pressure over 20 cm of Hg. This impairs arterial supply and block venous and lymph drainage, producing further damages abdominal organs. Immediate proper fluid management and abdominal surgery in needed to relive the high intra abdominal pressure.

Sudden Infant Death Syndrome (SIDS). A healthy newborn child suddenly stops breathing and dies during sleep. In majority of cases are due to suffocation due to putting children face down in a soft bed for sleep; which favors obstruction of mouth and nose. About 20 % cause remains unknown.

Thoracic outlet syndrome.

 Just below the clavicle at a point it turns towards the shoulder Subclavian artery and subclavian veins and all the nerves arise from the brachial plexus enter the chest wall and course down the medial side of the arm. There is just enough room for the structure to pass. In an abnormal situation like fracture of the clavicle and hematoma formation, a cervical rib and osteoma of the first rib that space becomes too tight for these structures and pressure on artery produce pain in the arm and hand, pressure on the vein swelling of hand and forearm and bluish discoloration of fingers, Pain over the nerve produces tingling numbness of fingers and muscle weakness. The pressure must be relived by surgery to prevent permanent damages to the hand.

Carpal tunnel syndrome.

 This is another syndrome like the thoracic outlet syndrome due to anatomical peculiarity at the flexer surface of the wrist. The median nerve on the way into the palm of the hand has to negotiate through a narrow passage in between wrist bones- Pisform laterally and Hammate and Capitate inferiorly and a strong transverse carpal ligament anterioly. Pain, specially at night , numbness and tingling are the initial symptoms felt in the hand and fingers, at times the pain is felt in the forearm. Later weakness of fingers and thumb, muscle atrophy and ultimately claw hand develops. The causes of Carpal tunnel syndrome are several - Unaccustomed weight bearing repeated flexion and extension of the wrist, pregnancy, fracture of wrist bones and malunion of fractures, synovitis of the flexor tendons, hypothyroidism and myxedema, rheumatoid arthritis, amyloidosis, sarcoidosis, acromegaly and leukemias.

Tarsal tunnel syndrome. Just like carpal tunnel syndrome,Tarsal tunnel syndrome may develop at the ankle joint. Symptoms and causes are practically same except for the site.

Inappropriate ADH secretion. Blood volume and serum osmolarity are maintained by feedback loops on the control center located in the hypothalamus and posterior pituitary gland. In lower blood volume and high sodium content of blood (high osmolarity) no Anti Diuretic Hormone (ADH) should be released from the posterior pituitary. But if ADH is still released in such condition, the situation is called Inappropriate ADH secretion. The causes are many, only important few will be mentioned here.

Syndrome X. Syndrome X is due to abnormal microcirculation of the coronary arteries or coronary vasospasm which results in Angina pectoris.

Syndrome of apparent mineralocorticoid excess, This syndrome is due to 11 beta hydroxysteroid dehydrogenase deficiency inherited on a autosomal recessive mode. Symptoms are early onset of hypertension in childhood, low serum potassium and metabolic alkalosis.

Metabolic syndrome. Metabolic syndrome is a more recent entry in syndrome category; previously the components of this symptoms were known as essential hypertension, hypercholesterolemia, obesity and diabetes mellitus. Under the new name those previous entities are refined and redefined, instead of hypercholesterolemia it is now low HDL cholesterol and high triglyceride. Obesity is now abdominal obesity, Diabetes is replaced by above impaired fasting blood glucose. People Metabolic syndrome are in high risk of developing coronary arterial disease, diabetes mellitus and cerebrovascular accidents.

Stokes - Adam syndrome. This syndrome is a well established a century ago, when physicians used their well cultivated skill of observation and taking pulse over several minutes. Main features of Stokes - Adam syndrome is sudden loss of consciousness and fall to the ground and having epileptic seizures due to complete heart block ( third degree in new definition) and pulse rate of 35 or below. Ventricular fibrillation and ventricular tachycardia also unconsciousness and seizures. At one time it was called Cardiac seizure and that name was better known than Stokes-Adam syndrome.

Long Q-T syndrome. This is an electrocardiogram finding. The time interval between the beginning of q wave and end of T wave on the tracing of an ECG (EKG) is normally 0. 43 millisecond when the heart rate in 72/ minute. In slower heart rate Q-T interval increases in a predictable way. In several cardiac diseases and quinine, procainamid, digitalis, over the counter cold medicines and many other medications can cause undue prolongation of Q-T interval. More longer the interval is there is more chance of Ventricular ectopic beats and precipitation of ventricular tachycardia and ventricular fibrillation. A particular form of multifocal and multi directional ectopic ventricular beats called Torsades des pointes (a French word, meaning twisting around points) is a forerunner of Ventricular fibrillation and death.

Torsades des pointes

Sick sinus syndrome. This is another very significant ECG finding. The natural cardiac pacemaker is the sinus node. In oxygen deprivation from any reason, electrolyte imbalance and certain medications, sinus node fails to generate the electrical pulse wave for heart muscle to contract. This can manifest as slow heart rate over 3 seconds, 1^st, 2^nd and 3^rd degree heart block. These changes are variable and in some cases variable cardic block can be intermittent. The detect the condition a special cardiac monitor is used, which can trace every cardiac beats and record on a preset program. This allows closer examination of any abnormal heart beat and suitable treatment can be offered – often a pacemaker. Main symptom of sick sinus syndrome is missing a heart beat, irregular pulse, palpitation, fluttering sensation in chest, confusion and loss of balance and fall.

Goodpasture syndrome. Goodpasture syndrome is an example how antibody, generated to fight an unidentifiable infection, mistakes its own kidneys as foreign and attacks the collagen tissue  present in the the basement membrane of glomeruli and walls of alvioli of lungs, results in hemorrhage in the kidney and lungs. Main symptoms are bloody urine and coughing out of blood. Other significant symptoms are shortness of breath, chest pain, fatigue , anemia, high BP, fatigue , nausea and vomiting. It is a major illness and requires immediate medical attention.

Alport syndrome. Alport syndrome is multisystem inherited disorder involving collagen IV tissue and results in renal failure, deafness and visual impairment. The defective gene is carried on X chromosome. Male child develops glomerulonephritis at early age and progresses rapidly and unless treated dies by age 40, females are less frequently affected and disease progress slowly.

Nephrotic syndrome. Nephrotic syndrome is a stage in renal failure arises from protein loosing glomerulonephritis. Presence of large amount of proteinin the urine amkes urine foamy, hypoalbumia produces puffy eyes, pale puffy face, ankle edema and scrotal edema. With the further progression of disease ascites and plural effusion are seen. Anemia, fatigue, weight gain from accumulated water develop. Intercurrent infection is common.

Carcinoid syndrome. In a previous blog, carcinoid syndrome was discussed in details. See foot note.

Carcinoid syndrome is due production of a number polypeptides  which have hormone like effects released from one variety of neuroendocrine tumor. Carcinoid tumors are generally arise in the small intestine, stomach, colon, appendix , rectum and liver and pancreas, and also arises in the bronchial tree of the lung. Carcinoid secrete serotonin, histamine, kallikrein, tachykinins and prostaglandin. These are potent vasodilators and produce intense vasodilatation, hypotension, watery diarrhea, asthma like bronchospasm and intense flushing of the face and body. The tumors are small and can be benign or malignant, but pathologically can not be determined whether a tumor is benign or maliganat. In malignant variety the tumor metastasize in the liver.

Dumping syndrome. Dumping syndrome is a number of gastrointestinal symptoms occur when a few minutes after a meal. Vagotomy and reducing stomach capacity by surgery are the principal causes of Dumping syndrome. Following any such stomach surgery, the food leaves the stomach prematurely and enters the duodenum in large amounts overstretching the duodenal wall causing upper abdominal crampy pain, sense of abdominal fullness, nausea, diarrhea, weakness and lightheadedness. And later develops palpitation and rapid heart beats.

Short bowel syndrome. Certain medical illnesses require taking out a part of the small intestine. The small intestine becomes shorter. This changes absorptive capacity of the small intestine and patients develop loss of weight and nutritional deficiency. Crohn disease and ischemic bowel are most common causes.

Zollinger-Ellsion syndrome ( Z-E Syndrome). Z-E syndrome is due to Gastrin producing tumor - Gastrinoma of the duodenum or pancreas. Gastrin stimulates gastric acid production. Majority of Z-E syndrome are spontaneous in origin but 25 % are due to Multiple endocrine neoplasm of type 1( MENS1). Several complication generally develop and are pretty serious – gastric perforation and profuse Gastric bleeding, esophagitis and esophageal atresia.

Budd Chiari syndrome. This syndrome is due to hepatic vein thrombosis which produces liver enlargement, upper abdominal pain, hepatic necrosis followed by cetrilobular fibrosis and jaundice and liver failure. Patients may develop this condition due to hypercoagulable state from inherited conditions like Factor V Leiden, Protein C and S deficiency or from acquired conditions like myeloproliferative disorders or Paroxysmal Nocturnal Hemoglobinuria.

Sjorgen syndrome. This syndrome is named after a Swedish physicians Dr Henrik Sjorgen who reported cases of chronic arthritis associated with dry eyes and dry mouth. It is an autoimmune disease producing chronic lymphocytic inflammation of salivary and lacrymal glands. The microvascular and ductal blockage results from inflammation produce dryness. In addition, exocrine glands of the skin, GI tract, joints, lungs, CNS and kidneys are involved. Arthritis of the hand resemble rheumatoid arthritis. ANA blood test is positive over 1:256 dilution and in addition SS-A, SS-B and RP serology are positive. Sjorgen patients run risk of B-cell lymphoma (non-Hodgkin lymphoma)and antiphospholipid antibody production results in vascular thrombosis.

Gullian Barry syndrome. This is an example of Autoimmune nervous system disease. Antibodies attack myelin sheath of the peripheral nerve and damaged sheath eventually damages the core nerve fibers of axons. Peripheral neuritis causes weakness of muscles of limbs, muscles of respiration and face. What triggers antibody production is not known but a viral infection is likely. From the onset of symptoms of muscle weakness and tingling numbness and pain, the disabilities reaches maximum in 3 weeks and respiratory failure develops.

Pickiwian syndrome. Nearly 200 years ago, Author Charles Dickens in his famous publication “The posthumous papers of the Pickwick club” described obese individual awake but hypoventilate due to reduced sensitivity to hypercapnia of the respiratory center and frequently dowsed off. Pickiwian syndrome is chosen to honor Dickens's astute observation of human nature. People with this syndrome have BMI over 30Kg/square M. Fat accumulates around neck, chest and upper abdomen, have blunt respiration drive even in presence of the strongest stimulus- respiratory acidosis and hypercapnia. Laptin insensitivity explaining the reason for obesity.

Premenstrual syndrome. Million of women suffers irritability, mood changes, weight gain and puffiness of face and hands and feet before the menstrual flow begins. These symptoms are due to hormonal changes necessary to induce shedding of extra growth of endometrium which developed in anticipation of fertilization of a ovum and the beginning of pregnancy.

Congenital Myesthenia syndrome. This syndrome is inherited by autosomal recessive pattern, and also rarely by autosomal dominant mode. Weakness of muscles of the eyelids, eye muscles that moves the eyes, muscles of chewing and swallowing are commonly affected. Repeated movements make weakness worse. Mutation of CHRN gene is responsible for over 50 % of cases, the rest of the cases are due to mutation of RAPSN, CHT, COLQ DBC7 genes. Children fails to suck breast milk. Swallowing and any normal physical activities are affected. Severity of disabilities varies depending upon the mutated genes. All these genes are responsible to provide codes of protein synthesis required for normal functioning of transmission of nerve signal across the neuromuscular junction.

Eaton-Lambert syndrome. Eaton-Lambert syndrome is an autoimmune disease. Immune system produces antibodies which mistakenly attack the Calcium Channels on the nerve endings. This results in fewer functional pathways for nerves to deliver signals to the effector sites involving both somatic and autonomic nervous system. In construst with Myesthenic syndrome, repeated action improves muscle functioning. Small cell carcinoma of the lung is the most commonly responsible for this syndrome, other malignancy also can produce this syndrome. The leg muscles are commonly affected, the effects of autonomic nervous system can be severe in cardiovascular system and urogenital system.

Wernicki - Korsakoff syndrome. This syndrome is a combination of Wernicki encephalopathy and Korsakoff psychosis. Chronic alcohol abuse is the underlying cause of Vitamin B1 deficiency which the cause of this syndrome however, other nutritional deficiency are associated. The symptoms are - inability to develop memory of current events, confabulation and talkativeness, lethargy, confusion and coma. MRI shows atrophy of the thalamus, hippocampus, hypothalamus and enlarged ventricles. The symptoms are reversible if treatment can be started before Wernicki encephalopathy sets in.

Ramsey Hunt syndrome. This is a special case of Shingles. The one side of the face develop palsy of lower motor neuron type and is associated with vesicular rashes on external auditory canal, pinna, mucous membrane of the oropharynx . This is due to reactivation of Vericella - zoster virus (chicken pox virus). The symptoms are pain in the ear, deafness, tinnitus, vertigo, balance and ambulatory difficulties.

Loefflers syndrome. Loefflers syndrome is due to very high eosinophil count in the blood associated with infiltrate of eosinophils in the lung tissue producing pneumonia like symptoms and bronchospasm. In early days it was due to ascaris lumbricoides parasitic infestation when ascaris larvae wondered around to find its fianl residing place in the small intestine. The alergic reaction generated an eosinophilic immune reaction. Now other parasites are known to produce similar reactions during their tissue migration.

Waterhouse- Federick syndrome. Waterhouse-Federick syndrome is a real emergency situation during a miningococcacal meningitis with bilateral adrenal hemorrhage due to toxemia. It produces acute adrenal insufficiency manifested as shock, hypotension, vascular collapse and cerebral, renal and pulmonary inefficiencies. Many other bacterial and viral infection are also known can also produce this syndrome. Immediate intervention to normalize blood volume and tissue oxygenation must be instituted and intravenous corticosteroids admistration is administered along with antibiotics and other therapeutic agents.

Gilbert syndrome. This is an inherited benign liver condition involving high blood unconjugated bilirubin level causing jaundice. Other parameter of liver functions are all normal and no treatment is required.

Osler-Weber- Rendu syndrome. This is also known as Heriditory Hemorrhagic Telangectasia. This inherited in an autosomal dominant mode. It is due to presence of multiple gene mutations. Arteriovenous malformation is present on skin, mainly on the face and mucous membrane of nose, mouth , stomach, GI tract, liver, lungs, spinal cord and brain. Bleeding from involved organs can produce a wide varieties of symptoms, bleeding in the brain can be fatal.

Footnote: For further reading see https://humihealth.blogspot.com/Medical matters.

1. Carcinoid syndrome, - Carcinoid and Neuroendocrine tumors. Blog. Medical matters dated 13 june 2011.  2. Loefflers syndrome. - Round worm Ascaris lumbricoides.Dec 6.2023 3. Korsakoff psychosis. - Speech disorder. Oct,16,202.    4. Sjorgen syndrome. - Collagen & mixed connective Tissue diseases.Dcc14,2022.    5.Zollinger- Ellison synfrome. - Perptic ulcers.Feb 16, 2023   .6.Polycystic Ovary syndrome.Insulin resistanceMarch10,2022.         7. Cushings synrome. Pituitary gland. August 20,2021. + Adrenal gland Oct22,2021.                                             8.Rumsey Hunt syndrome. Chicken pox Feb16,2023,    9.Myesthenic syndrome.Neuromusculat transmission, Dec22,2022.   10. Milk- Alkali syndrome. Kidney stones April16,2022.

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