Disorders of Coagulation

Hemophilia A and B (Christmas disease) are sex-linked recessive diseases caused by a deficiency of clotting factor VIII and IX, respectively. They are major causes of childhood intracerebral hemorrhages. In inherited hypercoagulability, mutation of coagulation factor V gene (factor Leiden) has been associated with ischemic strokes in children. Diseases with protein-C, protein-S, and antithrombin-III deficiencies are inherited in an autosomal dominant pattern. They affect young adults and...

Clinical Features

NPH occurs in individuals 60 to 70 years of age or older. The clinical criteria include the triad of progressive gait disorder, often the presenting symptom dementia and urinary incontinence. The gait disorder manifests with short shuffling steps and postural instability (frontal gait apraxia). The dementia has components of frontal lobe dysfunction psychomotor slowing, loss of initiative, and apathy. Spasticity in the legs and the appearance of Babinski sign may develop due to stretching of...

Infectious Vasculitis

A number of bacteria and fungi that infect the nervous system often produce an acute inflammatory, necrotizing, or chronic granulomatous vasculitis of the cerebral blood vessels. Spirochetes may infect the blood vessels Treponema pallidum in neurosyphilis and Borrelia burgdorferi in Lyme disease. HIV-associated vasculitis is prone to cause ischemic episodes in both adults and children. Vasculitis of the large cerebral arteries accounts for the hemiplegia that develops contralaterally to a...

Cytomegalovirus Infection

Neurologic diseases associated with cytomegalovirus infection are more often encountered in immunocom-promised particularly HIV-infected patients. The infection is acquired by exposure to infected saliva or respiratory secretion, transfusion, and possibly by sexual contact. Fetuses are infected by transplacental transmission and, neonates are infected by feeding with infected breast milk. Acute infections have a broad spectrum of clinical-pathological presentations aseptic meningitis...

Congenital Disorders of Glycosylation

Congenital disorders of glycosylation (CDG), a group of autosomal recessive multisystem disorders, is caused by deficient activity of enzymes involved in glycosylation of proteins. Several carbohydrate-deficient glycoprotein diseases have been distinguished. Among them, CDG type Ia is the most common. It is caused by the deficient activity of the enzyme phosphomannomutase. The mutant gene maps to chromosome 16. The disease affects chiefly infants and children and presents with many and various...

Herpesvirus Infections

The family of human herpesviruses encompasses the following important DNA viruses with strong affinity for the nervous tissue Herpes simplex type 1 virus (HSV-1) Herpes simplex type-2 virus (HSV-2) Varicella zoster virus (VZV) Human herpes viruses 6 and 7 (HHV 6 and 7) They are all major causes of sporadic infections. Herpesviruses, distributed worldwide, may infect the fetus in utero, neonates, and individuals of all ages. The initial infection may be inapparent or mild, producing fever,...

Meningovascular Syphilis

Meningovascular syphilis manifests 5 to 7 years after the initial infection and presents with meningeal and multifocal cerebral and or spinal cord symptoms and signs. The pathology is characterized by a proliferative endarteritis of the small, medium, and large arteries (Heubner endarteritis). A prominent endothelial proliferation along with mononuclear cell infiltrates in the media and adventitia lead to severe luminal narrowing and, eventually, occlusion and subsequent infarctions (Fig....

Herpes Simplex Virus1 Infection

Herpes simplex virus-1 infection is the major cause of sporadic and malignant encephalitis, chiefly in adults and young subjects. The infection is acquired by exposure to contaminated saliva or respiratory secretion. The virus initially causes a nasopharyngitis. By retrograde axonal transport, it reaches the trigeminal ganglia, where it becomes latent. Reactivation of the virus produces herpes vesicles on the lips (cold sore) or oral mucosa. The brain is infected by spread of the virus along...

Polyglucosan Diseases

This group of carbohydrate metabolic diseases is distinguished by the presence of polyglycosan bodies. These Galactosemia. A newborn boy was severely jaundiced, and his feeding was difficult because of frequent vomiting. In early childhood, his development was very slow and, after a few years, became arrested. At 7 years of age, he was physically underdeveloped and severely mentally retarded. Bilateral cataracts were diagnosed a few years later. He suffered from hypoglycemic episodes, frequent...

Echinococcosis

Echinococcosis (hydatoid disease) is acquired by the ingestion of food contaminated by eggs of Taenia echi-nococcus, a common intestinal parasite of dogs. The disease has a worldwide distribution and is prevalent in sheep- and cattle-breeding countries. The embryos reach the liver through the portal system through the systemic circulation, they reach the visceral organs, the brain and spinal cord, the skull, and vertebrae. Here they develop into cysts that contain Cerebral cysticercosis,...

Hereditary Neurometabolic Diseases

Lysosomal Diseases Peroxisomal Diseases Leukodystrophies Mitochondrial Diseases Amino Acid Metabolic Diseases Carbohydrates Metabolic Diseases Copper Metabolic Diseases Neuroaxonal Dystrophies Miscellaneous Neurometabolic Diseases Inherited neurometabolic diseases result from genetically determined defects in the biochemical processes of neural tissue, specifically, the deficient activity of enzymes or activator proteins. A group of diseases is caused by dysfunctions of the cellular organ-elles...

Mucopolysaccharidoses

Mucopolysaccharides (MPS) or glycosaminoglycans (GAGs) consist of polysaccharide chains attached to a polypeptide core. Due to deficient activities of specific enzymes, MPSs accumulate in visceral organs and mesenchymal tissues and are excreted in urine. The mucopolysaccharides that are stored and excreted in urine are dermatan sulfate, heparan sulfate, and chon-droitin sulfate. Mucopolysaccharidoses, common lysosomal diseases, affect chiefly infants and young children and are transmitted in an...

Hereditary Metabolic Diseases

Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS), a maternally Complication of anticoagulation. A. CT scan of a 73-year-old man treated with Coumadin for chronic atrial fibrillation shows a recent left parietal infarct. B. CT scan repeated 3 days later because of mental changes shows an acute hemorrhage within the infarct. Complication of anticoagulation. A. CT scan of a 73-year-old man treated with Coumadin for chronic atrial fibrillation shows a recent...

Ft VV I Vf

The amyloid core is surrounded by argyrophilic filamentous, rod-shaped, and granular structures derived from dystrophic neuronal processes and presynaptic terminals. They immunoreact for tau protein (see Fig. 5.5). A variable number of reactive astrocytes and activated microglial cells surround the dystrophic neurites (see Fig. 5.5). A burnt-out or compact plaque contains only an amyloid core (Fig. 5.6). Neurofibrillary tangles. These argyrophilic structures within the...

Cockayne Syndrome

Cockayne syndrome, a rare autosomal recessive disorder, is caused by mutations in either the CSA or CSB gene. The disease manifests with dwarfism microcephaly facial dysmorphism with prognathism, malformed large ears, enophthalmos, and beaked nose long extremities and sensitivity to sunlight. Neurologic abnormalities are mental retardation, sensorineuronal hearing impairment, optic atrophy and pigmentary retinal degeneration, myoclonus, and pyramidal and extrapyramidal symptoms and signs....

V

Burnt-out neuritic plaque consists of amyloid core only, lacking dystrophic neurites (Bodian stain). Neuronal degeneration results in deficiencies of the major neurotransmitters. Neuronal losses in the basal nucleus of Meynert are responsible for deficiencies of acetylcholine and its enzyme, choline acetyltransferase in limbic and neocortical areas. Cholinergic deficiency is strongly implicated in the memory deficit of AD. Neuronal losses in the locus ceruleus account for...

Dementias

Dementia is defined as impairment in short- and long-term memory, associated with impairment in abstract thinking and judgment, other disturbances of higher cortical function, and personality changes. The disturbance is severe enough to interfere significantly with work or usual social activities or relationships with others. The diagnosis of dementia is not made if these symptoms occur in patients with altered levels of consciousness (Diagnostic and Statistical Manual of Mental Disorders, 4th...

Other Conditions Iatrogenic Complications

Diagnostic procedures and major surgeries for coronary artery and valvular diseases, heart transplant, and various organ and bone marrow transplants carry the highest risk for cerebral hemorrhage and infarction. Subdural and intracranial hemorrhages are rare compli cations of spinal anesthesia. Chiropractic manipulation of the neck poses a potential risk for the dissection of vertebral and carotid arteries. Among prescription drugs, anticoagulants and fibri-nolytic agents carry the risk of...

Gauchers Disease

Gaucher's disease, a systemic lipidosis, is caused by deficient activity of the enzyme P-glucosidase, encoded by a gene located on chromosome 1. Subsequently, gluco-cerebrosides accumulate in the visceral organs and the brain. Among the three clinical phenotypes, the nervous system is affected in type 2 and type 3. Hepatospleno-megaly is evident in both. In infants, type 2 presents with bulbar symptoms, strabismus, and pyramidal and extrapyramidal symptoms. The clinical course averages 3 to 4...

Galactosemia

This is a rare autosomal recessive disorder of newborns. Importantly, if diagnosed early, it is effectively treatable. Galactose in the normal metabolic pathway is converted to glucose in four steps, each step being catalyzed by a specific enzyme. In galactosemia, the conversion of exogenous galactose to glucose is blocked in step two due to a deficiency of the enzyme galactose-1-phosphate uridyl transferase (GALT). As a result, galactose-1-phosphate, a metabolite from step one, accumulates in...

HIV Infection in Children

An estimated 3 million children are infected with HIV, and an estimated 13 to 23 of these children develop an encephalitis characterized by nodules of microglial cells and multinucleated giant cells similar to those in infected adults. Perivascular lymphocytic infiltrations are prominent. In addition, vascular and parenchymal Vascular mineralization in childhood HIV infection (HE). Vascular mineralization in childhood HIV infection (HE). mineralization occurs in the basal ganglia and white...

Syphilitic Infections

The incidence of infection with the spirochete Trepo-nema pallidum is rising among individuals infected with HIV and in those who abuse illicit substances. The disease is acquired by venereal contact. In about 40 of cases, the spirochetes infect the nervous system via the bloodstream within several weeks to several months after the initial infection and produce a menin-geal reaction. This may remain clinically asymptomatic and is diagnosed only by a positive serology test of the CSF....

Pathology

The brunt of pathology falls on the cerebellum, peripheral nerves, and spinal cord. The cerebellar pathology is confined to the dentate nuclei, which show extensive neuronal losses. Purkinje cell degeneration is usually mild. The peripheral nerves and sensory nerve roots show axonal and myelin degeneration, and the sensory spinal ganglia show neuronal losses. In the spinal cord, the posterior columns, the dorsal and ventral spinocer-ebellar tracts, the neurons in the Clarke's columns, and the...

Disorders of Red and White Blood Cells

Sickle cell anemia, an inherited hemoglobin disorder, is characterized by the replacement of hemoglobin A (HbA) with hemoglobin S (HbS sickle hemoglobin). Homozygotes have all HbA replaced with HbS (HbSS) and carry the disease, whereas heterozygotes have less than 40 HbS (HbSA) and carry the sickle cell trait. HbSA occurs in about 8 to 10 of African Siderocalcinosis of blood vessels in globus pallidus. Basophilic mineral deposits A. in the intima and media (HE), B. in full thickness of the...

Measles Virus Associated Diseases

Subacute Sclerosing Panencephalitis (SSPE) The disease develops several years after an acute systemic measles infection. It is suggested that the risk is higher for those who had measles or measles immunization at a very early age. SSPE affects primarily children and adolescents. Behavioral changes, slowly progressive mental regression, seizures, myoclonus, and focal neurologic deficits characterize the clinical picture. In the acute stage, EEG often shows a burst-suppression pattern of...

Histologic Features Neuronal Necrosis

Red neurons, the histologic hallmarks of hypoxic-ischemic injuries, display bright eosinophilia of the perikaryon, loss of Nissl substance, and shrunken baso-philic homogenous nucleus (Fig 3.3). Other neurons appear as ghost neurons, displaying faintly stained peri-karyon and nucleus, or as dark neurons, displaying condensed, darkly stained perikaryon and corkscrew- Hypoxic-ischemic neurons in (A) Ammon's horn and (B) cerebellar cortex. The perikaryon, shrunken and devoid of Nissl substance,...

Bibliography

D., & Love, B. B. (Eds.). (1994). Stroke in children and young adults. Boston Butterworth-Heinemann. Bogousslavsky, J., & Caplan, L. R. (Eds.). (2001). Stroke syndrome, 2nd ed. Cambridge, U.K. Cambridge University Press. Caplan, L. R. (1993). Stroke a clinical approach, 2nd ed. Boston Butterworth-Heinemann. Fisher, M. (Ed.) (1994). Clinical atlas of cerebrovascular disorders. London Mosby. Garcia, J. H. (1992). The evolution of brain infarcts a review. J...

Hypoglycemic Encephalopathy

The brain's metabolism depends on a constant and adequate supply of glucose, because only small amounts of it are stored. A sudden drop in the blood glucose level to 30 to 40 mg 100 mL results in permanent brain damage within 1 to 2 hours. Major causes of hypogly-cemic episodes are insulin overdose in diabetic patients, Hepatic encephalopathy in a 53-year-old chronic alcoholic man with severe liver cirrhosis. Alzheimer type 2 astrocytes in basal ganglia display (A) large vesicular nuclei,...

Spontaneous Intracerebral Hematoma

The majority of intracerebral hemorrhages are associated with hypertension, which affects the small parenchymal arteries and arterioles and leads to fibrosis, hyalinosis, and fibrinoid necrosis. Such diseased arteri-oles easily rupture, causing the hemorrhage. Less common causes of hemorrhages are vascular malformations, vasculopathies, hemorrhagic diseases, and hemorrhage within tumors (see Table 4.10 also see the section, Various Stroke Etiologies). Hypertensive hemorrhages have predilections...

Myelin

Myelin ensheathes the nerve fibers in a spiral lamellar fashion, promoting a faster and more effective conduction of nervous impulses along the nerve fibers. It is produced by the oligodendrocytes during development of the brain and spinal cord and maintained by them after completion of myelination (Fig. 2.10). The major chemical components of myelin are lipids, which constitute about 70 to 85 . The sphingolipids and cholesterol are the most important of these. The remaining 15 to 30 of myelin...

Astrocytic Tumors

Astrocytic tumors constitute the largest group of intracranial tumors in both adults and children. Their locations, gross and histologic features, biologic behavior, and genetic alterations vary greatly. The WHO distinguishes four grades of astrocytic tumors based on their histologic characteristics (Table 11.5). Astrocytic Tumors (Grades 2, 3, and 4) Diffuse astrocytoma grade 2, anaplastic astrocytoma grade 3, and glioblastoma grade 4 constitute the largest group of primary intracranial tumors...

Ischemic Stroke Cerebral Infarction

The brain requires a constant and adequate blood flow to supply oxygen and glucose essential for its high energy metabolism. A constant blood flow is assured by an autoregulatory mechanism of arteries and arterioles they constrict in response to rising systemic blood pressure and dilate in response to falling systemic blood pressure. This mechanism operates while the arterial pressure remains between 50 and 160 mm Hg. One- Atherosclerosis of cerebral arteries. A. Severe atheromatosis of basal...

1

Is depleted of neurons, becomes spongy, and displays a dense astrofibrosis. The white matter is variably devoid of myelin, which is replaced by astrogliosis. Astrocytes in the cerebral cortex and oligodendrocytes in the white matter may display argyrophilic and tau-immunoreactive cytoplasmic inclusions. Dementia with Parkinsonism Linked to Chromosome 17 Clinical features. This is a familial dementia inherited in an autosomal dominant pattern The interest of the disease lies in its association...

Intracranial Hemorrhages

Intracranial hemorrhages may occur in the epidural, subdural, and subarachnoid compartments and within the brain parenchyma. Epidural hematoma EDH occurs in 2 of severe head injuries. An epidural hematoma forms between the inner table of the calvarium and the dura, usually in the frontotemporal region Fig. 12.1 . It is commonly an arterial bleed that results from tearing of meningeal arteries, often of the middle meningeal artery, by a linear fracture across its cranial groove. In children, it...

Spinal and Spinal Cord Defects

Vertebral Defects

Dysraphic disorders of the spine and spinal cord comprise a broad spectrum of malformations, ranging from total absence of the cord to asymptomatic bony defects and cord anomalies. Familial occurrences are common. The clinical manifestations vary from mild motor and sensory deficits to paraplegia with severe sensory impairment and loss of sphincter control. Amyelia, total absence of the spinal cord occurs with anencephaly see Fig. 13.2 . The cord is replaced with a mixture of fibrous tissue,...

Heterotopia

Heterotopia are groups of neurons displaced in the cerebral hemispheric white matter Fig. 13.19 . Common sites are the periventricular zones, centum semiovale, and the subcortical white matter. Rarely, tiny groups of neurons form nodules on the cortical surface brain warts . Neuroglial nests may also occur in the leptomeninges. . 111111M M IM1J I I II IM 1111L111111 I J t M11111111M I 1111 1111M I 11111 I lt 11 1111M I k Heterotopia. A 10-year-old mentally retarded epileptic boy. A. Nodular...