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