Endocrine diseases

Disorders of the hypothalamus can result in autonomic dysfunction, sleep disturbance, and diabetes insipidus. Pituitary tumours may cause acromegaly, which may result in peripheral-nerve compression. Hyperactivity of the thyroid gland may cause tremors, muscle weakness, and disturbances of eye movement, while hypoactivity may result in mental dulling, deafness, muscle stiffness, and median-nerve compression. Muscle weakness is a symptom of the parathyroid gland hyperactivity; hypoactivity may cause seizures. Muscle weakness is also a feature of adrenal gland dysfunction in both Addison and Cushing diseases; both of these conditions also induce abnormal mental states.

Diabetes mellitus causes many neurological complications, including peripheral neuropathy, autonomic system failure, painful nerve root lesions in the lumbosacral plexus, atherosclerosis, stroke, and damage to the retinas. Hyperinsulinism reduces blood sugar levels, which may cause coma.

Organ failure

When the function of the liver, lung, heart, or kidney fails, the nervous system is affected. With liver failure dementia, confusion, aphasia, dysarthria, tremors of the limbs, and coma may result.

Kidney failure is often associated with high blood pressure, which may lead to acute brain edema (distension with fluid), visual loss, and coma. Chronic kidney failure is likely to produce peripheral neuropathy as well as symptoms similar to those of liver failure but with increased likelihood of epileptic seizures.

Chronic respiratory or heart failure also can cause confusion and raised intracranial pressure. In addition to these symptoms, respiratory failure may cause tremors.

Blood diseases

Leukemia and polycythemia can affect the nervous system, the former mainly through infiltration of the meninges or brain and the latter by increasing the risk of stroke. Anemia due to deficiency of vitamin B₁₂ may cause spinal cord degeneration and stroke.

Protein and amino acid disorders

Phenylketonuria (PKU) is a disorder of the conversion of the amino acid phenylalanine (a building block of protein) into tyrosine. The primary result is a delay in mental and motor development. PKU can be diagnosed within days of birth by a simple urine test and is treated with a diet low in phenylalanine, which may allow intellectual development to proceed. Other aminoacidurias, which cause psychomotor delay and a variety of neurological and musculoskeletal problems, include hyperglycinemia, hyperammonemia, Hartnup and Lowe diseases, maple syrup urine disease (so called because of the distinctive smell of the urine), and homocystinuria (a condition that predisposes one to strokes).

Disorders of fat and fatty acid metabolism

Lysosomal diseases are caused by the accumulation of substances that are normally metabolized in the cellular structures called lysosomes. These disorders often produce symptoms of neurological involvement at birth or in the early years of childhood.

Many of the conditions mentioned in this and the next section are caused by a genetically determined enzyme failure within cells, which leads to the accumulation of substances that would normally be metabolized. These conditions are called lysosomal disorders after the lysosome, the structure in the cell that contains these substances, and often produce symptoms of neurological involvement at birth or in the early years of childhood. Examples of lysosomal disorders include Tay-Sachs disease, metachromatic leukodystrophy, Krabbe disease, Fabry disease, Gaucher disease, Farber disease, and Niemann-Pick disease. Psychomotor retardation, seizures, retinal abnormalities, peripheral neuropathies, and musculoskeletal deformities are prominent features of these diseases. Other lysosomal disorders, called sudanophilic leukodystrophies, are characterized by defective formation of myelin and cerebellar and corticospinal tract dysfunction. Adrenoleukodystrophy occurs only in males and leads to blindness, motor weakness, spasticity, and signs of adrenal gland failure. In Refsum syndrome peripheral neuropathy and retinal and cerebellar disorders accompany a dry, scaly skin rash. The restriction of dietary phytanic acid, a substance found in green vegetables, slows the progress of the disease.

Inherited deficiencies of blood lipoproteins also may result in peripheral neuropathy, retinal degeneration, and other motor and skeletal deformities. In analphalipoproteinemia, the tonsils are swollen with accumulations of cholesterol, while in betalipoproteinemia, excessive fat is present in the stools. Lipofuscinosis is a disorder in which lipids are stored in the retinas and nervous system, causing visual impairment, seizures, intellectual decline, and spastic weakness.

Disorders of carbohydrate metabolism

Galactosemia develops when infants are unable to metabolize galactose, or milk sugar. Cataracts, weakness of the limbs, and psychomotor delay occur unless substitutes for milk are given. In glycogen-storage diseases glycogen cannot be metabolized to yield lactic acid and energy, so that it accumulates within muscle, liver, and other tissues. In mucopolysaccharidoses and mucolipidoses (both lysosomal disorders), fat and carbohydrates are deposited in the nervous system and in other tissues; severe intellectual disability, motor and ocular disorders, and skeletal abnormalities are common features.

Deficiency states

Vitamin A deficiency primarily affects the retinas and skin, but components of the vitamin B group are essential for normal development and functioning of the nervous system. Wernicke-Korsakoff syndrome (common in alcoholics) results from a thiamine (vitamin B₁) deficiency and consists of eye movement disorders, cerebellar incoordination, memory loss, and peripheral neuropathy. If peripheral neuropathy is the only symptom of thiamine deficiency, the disorder is called beriberi. In each case, replacement of the vitamin may lead to substantial improvement. When other vitamins (e.g., niacin, pyridoxine) are deficient, symptoms are similar, and signs of spinal cord disease may occur.

Subacute necrotizing encephalopathy, also called Leigh disease, is a lethal disorder of infancy marked by psychomotor delay, myoclonic jerks, paralyses of eye movements, and respiratory disorders. The precise biochemical defect is unknown, but thiamine metabolism dysfunction may be involved. Seizures in early childhood are the main feature of pyridoxine (vitamin B₆) dependency, an inherited abnormal metabolic requirement for that vitamin.

Vitamin D deficiency may cause the softening of bone, called rickets, may affect the nervous system, and may cause weakness of the proximal muscles.