SYSTEMIC DISEASES AND GENERAL MEDICINE

1. SYSTEMIC DISEASES AND GENERAL MEDICINE Prof. Dr. Sibel ERTAN

2. Endocrine diseases • Hypothyroidism • Hyperthyroidism • Hypoparathyroidism • Hyperparathyroidism • Diabetes mellitus • Hypoadrenalism • Hyperadrenalism

3. 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

4. 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

5. Hyperthyroidism The neurologic complications of hyperthyroidism include: • 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

6. 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

7. 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

8. Diabetes mellitus Primary neurologic complications of DM: • Peripheral neuropathy (mononeuropathies, polyneuropathy, autonomic neuropathy, radiculopathies, entrapment neuropthy) • Hypoglycemic coma • Stroke

9. 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

10. 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%)

11. 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

12. 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

13. 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

14. 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

15. 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

16. 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

17. Hereditary abnormalities of fibrinolysis • Plasminogen deficiency • Tissue plasminogen activator deficiency • Dysfibrinogenemia • Factor XII deficiency

18. 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

19. Paraneoplastic syndromes A praneoplastic syndrome is one that occurs more frequently than expected by chance in association with neoplasm, most often a malignant tumor

20. 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

21. 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

22. 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 isbound 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

23. 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

24. 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.

25. 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