SYSTEMIC DISEASES AND GENERAL MEDICINE Prof. Dr. Sibel ERTAN.
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Transcript of SYSTEMIC DISEASES AND GENERAL MEDICINE Prof. Dr. Sibel ERTAN.
SYSTEMIC DISEASES AND GENERAL MEDICINE
Prof. Dr. Sibel ERTAN
Endocrine diseases
Hypothyroidism Hyperthyroidism Hypoparathyroidism Hyperparathyroidism Diabetes mellitus Hypoadrenalism Hyperadrenalism
Hypothyroidism
The neurologic complications of hypothyroidism
include: Headache Disorders of cranial and peripheral nerves Sensorimotor abnormalities Changes in cognition and level of
consciousness Cerebellar syndrome
Hypothyroidism
Chracteristic findings:
Low circulating T4 and T3, elevated TSH levels Low radioiodine uptake by the thyroid Increase of the CSF protein content (values greater than 100 mg/mL are not
exceptional) EEG abnormalities include slowing and
generalized decrease in amplitude
Hyperthyroidism
The neurologic complications of hyperthyroidisminclude: Tremor Thyrotoxic myopathy (weakness and wasting of the muscles
of the pelvic girdle to a lesser extent of the shoulder girdle. DTRes are normal or hyperactive. Fasciculations and myokymia may be noted) Thyrotoxic myopathy needs to be distinguished from
myasthenia gravis Stroke (abnormal cardiovascular and autonomic functions) Mental disturbances (from mild irritability to psychosis) Graves ophthalmopathy
Hypoparathyroidism
The neurologic complications of hypoparathyroidism
include:
Mental deficiency Tetany (In latent tetany:Chvostek sign, Trousseau sign, Erb sign) Seizures Hyper- or hypokinetic movement disorders (intracranial
calcifications) Increased intracranial pressure with papiledema Hypoparathyroid myopathy
Hyperparathyroidism
The neurologic complications of hyperparathyroidism
include:
Symmetric proximal limb weakness and muscle wasting
DTRes are normal or hyperactive Chorea, abnormal movements of the tongue Mental status changes (memory loss, irritability) Depression
Diabetes mellitus
Primary neurologic complications of DM:
Peripheral neuropathy (mononeuropathies, polyneuropathy, autonomic
neuropathy, radiculopathies, entrapment neuropthy) Hypoglycemic coma Stroke
Hematologic and related diseases
Polycythemia Heparin-induced Thrombocytopenia Leukemia Antitrombin III deficiency Protein S deficiency Protein C deficiency Factor V Leiden mutation Hereditary abnormalities of fibrinolysis Autoantibodies Hemophilia
Polycythemia Headache due to increase of the blood viscosity In 50% to 80% of patients:
dizziness, tinnitus, visual disturbances, cognitive impairment
Predisposes to large and small vessel cerebral infarction and may accelerate atherosclerosis
Thrombocytosis and a platelet disorder that leads to a hemorrhagic diathesis may be seen
Peripheral neuropathy (predominantly sensory axonal, in up to 46%)
Heparin-induced Thrombocytopenia
Immune-mediated disorder The pathogenic IgG binds a heparin/platelet
factor 4 complex platelet activation. Platelet account by 50% or greater 50% of patients develop thrombotic
complications. Cerebral infarctions in 3%-4% of patients Heparin should be stopped, warfarin
withheld
Leukemia Indirectly
Therapy complications (hemorrhage due to thrombocytopenia or infections due to white blood cell count)
Leukostasis (>150,000/mm3) may occlude cerebral blood vessels)
Directly In acute myelogenous leukemias CNS involvement
is uncommonly the first manifestations Acute lymphocytic leukemia involves the CNS in
5% to 10% of patients at the time of diagnosis, often without symptoms
Chronic leukemia rarely affects the CNS
Antithrombin III deficiency
Plasma glycoprotein (synthesized by the liver and endothelial cells)
ATIII is required for the anticoagulant action of heparin Heparin accelerates the inactivation of factor Xa and
thrombin Most common presentation is leg thrombosis and
pulmonary embolus Cerebral venous thrombosis is more common but arterial
thrombosis may occur ATIII deficiency is resistant to anticoagulation with heparin After a thrombotic event, lifelong warfarin therapy is
indicated
Protein S deficiency
Protein S is a vitamin K-dependent plasma protein PS is synthesized in the liver PS facilitates the binding of protein C to the platelet
membrane (acting as a nonenzymatic cofactor for the anticoagulant activity of activated protein C).
Only 40% of PS is in a free form The rest is in an inactive form, bound to C4-binding
protein. (C4-binding protein levels are elevated during acute inflammation or stress increasing the inactivation of PS)
Up to 20% of patients with stroke have PS deficiency
Protein C deficiency
Protein C is a vitamin K-dependent plasma protein
PC is synthesized in the liver PC is activated by thrombin-thrombomodulin
complex PS enhances the activity of PC PC inactivates factors Va and VIIIa PC deficiency is found in 6% to 8% of patients
who have a stroke before age 40
Factor V Leiden mutation
FVL is the most common known genetic risk factor for thrombosis
The incidence of heterozygous FVL is 2% to 8.5%.
A mutation of the FV gene results in factor Va resistance to degradation by activated protein C
Hereditary abnormalities of fibrinolysis
Plasminogen deficiency Tissue plasminogen activator
deficiency Dysfibrinogenemia Factor XII deficiency
Autoantibodies
Antiphopholipid antibodies, encompassing Lupus anticoagulant and anticardiolipin
antibodies are the most common acquired defects
associated with thrombosis May cause:
Ischemic strokes Cerebral venous sinus thrombosis Dementia Chorea
Paraneoplastic syndromes
A praneoplastic syndrome is one that occurs more frequently than
expected by chance in association with neoplasm, most often a
malignant tumor
Paraneoplastic syndromes
All syndromes are rare All syndromes together occur in less than 1%
of all patients with small cell lung cancer Conversely, among patients diagnosed with a
recognized PNPS 10% to 60% prove to have a tumor
Most PNPSs are autoimmune in origin
Paraneoplastic syndromes
Clinical neurologic syndromes Paraneoplastic cerebellar degeneration Subacute sebnsory neuropathy/encephalitis Limbic encephalitis Brainstem encephalitis Opsoclonus-myoclonus Myelitis Motor neuron diseases Sensorimotor peripheral Neuropathy Neuromuscular disorders Myopathies
Vitamin B12 deficiency
Animal products are the sole dietary sources of cobalamin for humans
Gastric acid is needed for peptic digestion to release the vitamin from proteins
The freed B12 is bound by R proteins and than by gastric intrinsic factor, produced by gastric parietal cells, which is needed for absorption of B12
Intrinsic factor-cobalamin complex is transported across the teminal ileum and binds to transcobalamin
The complex enters the cells by endocytosis, and the vitamin enters red blood cells in an energy dependent process
Cobalamin is converted to adenosyl or methyl coenzymes, which are necessary for normal neural metabolism
If they are missing, abnormal fatty acids may accumulate in myelin or methylating reactions may be defective
Vitamin B12 deficiency
About 80% of adult-onset pernicious anemia is attributed to lack of gastric intrinsic factor secondary to atrophic gastritis
The disorder is thought to be autoimmune in origin In the spinal cord white matter is affected more than gray Symmetric loss of myelin sheaths occurs more often than
axonal loss Changes are most prominent in the posterior and lateral
columns The thoracic cord is affected firstand than the process
extends in either direction Patchy demyelination may be seen in the frontal white
matter
Vitamin B12 deficiency
Clinical features:
40% of all patients with B12deficiency are said to have some neurologic symptoms or signs, and these are often the first or most prominent manifestations of the disease
Most patients are over 60 Most common symptoms are due to myelopathy or
neuropathy Memory loss, visual loss, orthostatic hypotension,
anosmia, impaired taste, sphincter symptoms, and impotance are other symptoms.
Vitamin B12 deficiency
The diagnosis rests on demonstration of blood levels of vitamin B12 less than 200 pg/mL, but low normal values (200-350 pg/mL) may be found in people who respond to therapy
In patients with neurologic signs, only about 20% show severe anemia
Both hematocrit and mean corpuscular volume may be normal
B12 is given intramuscularly in a dosage of 1000 g/day for the first week, followed by weekly injections for the first month, and then monthly injections for life