MENINGITIS

What is Encephalitis and Meningitis?
Encephalitis is an inflammation of the brain. There are many types of encephalitis, most of which are caused by viral infection. Symptoms include sudden fever, headache, vomiting, photophobia (abnormal visual sensitivity to light), stiff neck and back, confusion, drowsiness, clumsiness, unsteady gait, and irritability. Symptoms that require emergency treatment include loss of consciousness, poor responsiveness, seizures, muscle weakness, sudden severe dementia, memory loss, withdrawal from social interaction, and impaired judgement. Meningitis is an infection of the membranes (called meninges) that surround the brain and spinal cord. Symptoms, which may appear suddenly, often include high fever, severe and persistent headache, stiff neck, nausea, and vomiting. Changes in behavior such as confusion, sleepiness, and difficulty waking up are extremely important symptoms and may require emergency treatment. In infants symptoms of meningitis may include irritability or tiredness, poor feeding and fever. Meningitis may be caused by many different viruses and bacteria. Viral meningitis cases are usually self-limited to 10 days or less. Some types of meningitis can be deadly if not treated promptly. Anyone experiencing symptoms of meningitis or encephalitis should see a doctor immediately.

Is there any treatment?
Antiviral medications may be prescribed for herpes encephalitis or other severe viral infections. Antibiotics may be prescribed for bacterial infections. Anticonvulsants are used to prevent or treat seizures. Corticosteroids are used to reduce brain swelling and inflammation. Sedatives may be needed for irritability or restlessness. Over-the-counter medications may be used for fever and headache. Individuals with bacterial meningitis are usually hospitalized and treated with antibiotics. Antiviral drugs may also be prescribed.

What is the prognosis?
The prognosis for encephalitis varies. Some cases are mild, short and relatively benign and patients have full recovery. Other cases are severe, and permanent impairment or death is possible. The acute phase of encephalitis may last for 1 to 2 weeks, with gradual or sudden resolution of fever and neurological symptoms. Neurological symptoms may require many months before full recovery. With early diagnosis and prompt treatment, most patients recover from meningitis. However, in some cases, the disease progresses so rapidly that death occurs during the first 48 hours, despite early treatment.

What research is being done?
The NINDS supports and conducts research on infections and diseases of the brain and nervous system including encephalitis and meningitis. Much of this research is aimed at learning more about the cause(s), prevention, and treatment of these disorders.

Selected references

Pruitt, AA.
Infections of the Nervous System Neurology Clinics 16(2); 419-447 (1998).

Townsend, GC, and Scheld, WM.
Infections of the Central Nervous System Advances in Internal Medicine 43; 403-447 (1998).

Durand, M, et al.
Acute Bacterial Meningitis in Adults. The New England Journal of Medicine, 328:1; 21-28 (January 7, 1993).

Quagliarello, V, and Scheld, W.
Bacterial Meningitis: Pathogenesis, Pathophysiology, and Progress. The New England Journal of Medicine, 327:12; 864-872 (September 17, 1992).

Whitley, R.
Viral Encephalitis The New England Journal of Medicine, 323:4; 241-250 (July 26, 1990)

This fact sheet is in the public domain. You may copy it.

Provided by:
The National Institute of Neurological Disorders and Stroke
National Institutes of Health
Bethesda, MD 20892

LABORATORY FINDINGS

The diagnosis of CNS infection is made primarily by documentation of changes within the CSF obtained by lumbar puncture.  A deep yellow colour of spinal fluid is derived primarily from bilirubin pigment.  In the absence of haemorrhage, this is most frequently associated with elevated protein concentration and may be seen when the CSF circulation has been impaired.  Increased CSF protein generally accompanies an increase in white blood cells (WBC) and is the result of injury to the meninges by an inflammatory process and subsequent passive diffusion of albumin into the CSF from serum.  As few as 200 WBC/ul to 300 WBC/ul impart haziness to CSF; 500 WBC/ul give the CSF an opalescent appearance;  and 700 WBC/ul  to 800 WBC/ul cause a turbid appearance.   Fluid containing thousands of cells will look like pus.
Polymorphonuclear leukocytes predominate in bacterial infections, whereas lymphocytes predominate in tuberculous and nonbacterial infections.  A lack of cells does not invariably exclude the possibility of bacterial meningitis but this certainly is a rare occurrence.  Various stains (Gram's immunofluorescent,  acid-fast, auramine-rhodamine, india ink) and cultures on several media should be done on CSF to identify the pathogenic organism.  There is a decrease in CSF glucose in bacterial, tuberculous, mycotic, and carcinomatous meningitis.
Decreased CSF glucose is the result of increased glucose utilisation by rapidly growing microorganisms, phagocytosis of bacteria by WBC, and impaired glucose transport into the CSF from the bloodstream across the inflammatory exudate.

Acute Bacterial Meningitis

• CSF
• CSF appears opalescent to purulent. slightly yellow, and might have a course clot.
• Protein 50 mg/dl - 1500 mg/dl (usually 100 mg/dl - 500 mg/dl)
• Glucose 0 mg/dl - 40 mg/dl;  <31% of the blood glucose concentration
• WBC 100 ul to > 50,000/ul (usually 4,000/ul - 10,000/ul), 85% - 95% neutrophils; as the disease progesses there is a gradual increase in lymphocytes and large mononuclear cells.  Cell counts above 50,000/ul raise the possibility that a brain abscess has ruptured into the subarachnoid space.  (see Brain Abscess)
• One or more bacterial organisms are usually seen on a gram-stained smear and recovered on culture - usually Hemophilus influenzae, Neisseria meningitidis, Streptococcus pneumoniae; in newborns, Escherichia coli  and group B streptococci are frequently recovered.  Prior antibiotic treatment decreases the frequency of positive cultures.
• Through counterimmunoelectrophoresis and latex agglutination, soluble bacterial capsular antigens in CSF may be detected.  These tests are of great help for rapid diagnosis and also for diagnosis after treatment has been started and the smears and cultures are negative.  They are used to test for the antigens of meningococcus, pneumococcus, H. influenzae, and group B streptococci.
• Increased CSF lactate dehydrogenase (LDH), especially LDH4 and LDH5, which are derived from granulocytes

• Blood cultures are positive in 40% - 60% of patients with bacterial meningitis.
• Nasopharyngeal cultures often yield pathogenic H. influenzae or N. meningitidis.
• Leukocytosis with a shift to the left
• Markedly increased serum C-reactive protein

• CSF appears opalescent, slightly yellow;  a delicate clot may be seen
• Protein 45 mg/dl - 500 mg/dl (usually 100 mg/dl - 200 mg/dl)
• Glucose 10 mg/dl - 40 mg/dl;  not usually as low as in bacterial meningitis
• WBC 25/ul - 500/ul, chiefly lymphocytes; neutrophils may equal lymphocytes early in the infection
• Organisms may be seen on an acid-fast - or auramine-rhodamine-stained smear of the fibrin clot or pellicle and recovered on culture.
• Decreased serum sodium - this might be due to inappropriate secretion of antidiuretic hormone

• CSF appears normal.
• Protein 20 mg/dl - 50 mg/dl
• Glucose reduced in more than half of the cases
• WBC 0/ul-800/ul (average 50/ul), chiefly lymphocytes
• Identification of organisms on india ink or Nigrosin wet-mount preparation and isolation of Cryptococcus on culture
• Latex agglutination test of CSF and serum detects cryptococcal capsular antigen.  This is more sensitive than the use of india ink.
• Indirect immunofluorescence and tube agglutination tests for cryptococcal antibodies; these usually become positive after the latex agglutination test becomes negative

click on the image to view original. This is one of a series of Great images to be found on the linked page!

Fig. 2 Pyogenic Meningitis: This photomicrograph of subarachnoid space, in hematoxylin/eosin stain, shows the two components of an acute bacterial meningitis: polymorphonuclear leukocytes and fibrin, the latter arranged in meshes and strands (bottom of picture). The subarachnoid space is compromised, but not completely occluded.

For Original Image from the Virtual Hospital site click this link.

This section was stained with GMS, a silver stain which intensely stains the thick, gelatinous capsule of the cryptococcus. The other finding to note on this slide, which is also typical of fungal infections in the CNS, is the minimal inflammatory response relative to the number of organisms.

LABORATORY FINDINGS

CSF

• Clear, turbid, or xanthochromic
• Protein 20 mg/dl - 200 mg/dl (usually 80 mg/dl - 100 mg/dl)
• Glucose normal
• WBC <500/ul; chiefly neutrophils on the first day, then lymphocytes predominate; >1000 lymphocytes/ul usually occurs in lymphocytic choriomeningitis and may also occur with mumps and echovirus infections
• Negative bacterial smears and cultures
• Virus isolation

• Neutralisation viral serologic tests show a fourfold rise in titre from acute to convalescent sera;  the latter should be drawn 10 days to 2 weeks after the onset of illness.
• Indirect immunofluorescent test for lymphocytic choriomeningitis may become positive 3 days after the onset of symptoms.  Titres increase rapidly and decline slowly over several months.

Arboviruses

LABORATORY FINDINGS

CSF

• Early (first 2-3 days):  Cell count <100/ul, mostly neutrophils

Skin Biopsy

• Later (after 3rd day):  Cell count 50 ul - 500/ul, mostly lymphocytes

Blood

Viral serologic tests show fourfold increase in titre from acute to convalescent sera.
Haemagglutination inhibition and neutralisation antibodies are detected within 1 week after onset of symptoms and persist for at l east 8 years.
Complement-fixation antibodies first appear 2 to 3 weeks after onset and persist for 1 to 3 years.
Isolation of virus from blood and CSF of patients during the acute disease is unusual.

Herpes Simplex Virus

Link to this image no longer works (ref:www.healthcentral.com/ mhc/fullsize/2886.jpg)

Pathogenesis: Primary infection occurs through a break in the mucus membranes of the mouth or throat, via the eye or genitals or directly via minor abrasions in the skin. because of the universal distribution of the virus, most individuals are infected by 1-2 years of age; initial infection is usually asymptomatic, although there may be minor local vesicular lesions. Local multiplication ensues, followed by viraemia and systemic infection. There then follows life-long latent infection with periodic reactivation. During primary infection, the virus enters peripheral sensory nerves and migrates along axons to sensory nerve ganglia in the CNS - allows virus to escape immune response! During latent infection of nerve cells, viral DNA is maintained as an episome (not integrated) with limited expression of specific virus genes required for the maintenance of latency - true latency. The delicate balance of latency may be upset by various disturbances, physical (injury, U.V, hormones, etc) or psychological (stress, emotional upset - perhaps affecting immune system/hormonal balance). Reactivation of latent virus leads to recurrent disease - virus travels back down sensory nerves to surface of body and replicates, causing tissue damage:

LABORATORY FINDINGS

CSF

• Spinal fluid findings are similar to those described above for the arborvirus encephalitides.
• Fourfold rise in herpes antibodies in 80% - 85% of proven infections;  specificity ranges from 81% to 88%.  Ratio of herpes simplex virus antibodies in serum to the same antibodies in CSF is <20 by the 5th or 6th day of the disease.

• Herpesvirus may be cultured or identified by immunofluorescence, immunoperoxidase, or electron-microscopy techniques in 76% of cases.
• Culture of brain biopsy material is the most sensitive and specific diagnostic test

Click on image for link to original image and an excellent teaching page.

Chronic Inflammation, Viral Encephalitis: Note the brain post capillary venule cuffed by lymphocytes. This is an example of inflammation that arises with an initial lymphocytic response. It is acute in a temporal sense but the infiltrate contains few or no neutrophils. It is sometimes called chronic inflammation simply because of the lymphocytic infiltrate. Certain virus and bacteria preferentially elicit this type of initial response - probably because there are no chemotactic factors for neutrophils present.

Click here or on image for link to original article

Herpes zoster results from reactivation of the varicella-zoster virus. Unlike varicella (chickenpox), herpes zoster is a sporadic disease with an estimated lifetime incidence of 10 to 20 percent. The incidence of herpes zoster increases sharply with advancing age, roughly doubling in each decade past the age of 50 years. Herpes zoster is uncommon in persons less than 15 years old. In a recent study,1 patients more than 55 years of age accounted for more than 30 percent of herpes zoster cases despite representing only 8 percent of the study population. In this same study, children less than 14 years old represented only 5 percent of herpes zoster cases. The normal age-related decrease in cell-mediated immunity is thought to account for the increased incidence of varicella-zoster virus reactivation. Patients with disease states that affect cell-mediated immunity, such as human immunodeficiency virus (HIV) infection and certain malignancies, are also at increased risk. Chronic corticosteroid use, chemotherapy and radiation therapy may increase the risk of developing herpes zoster. The incidence of herpes zoster is up to 15 times higher in HIV-infected patients than in uninfected persons, and as many as 25 percent of patients with Hodgkin's lymphoma develop herpes zoster. The occurrence of herpes zoster in HIV-infected patients does not appear to increase the risk of acquired immunodeficiency syndrome (AIDS) and is less dependent on the CD4 count than AIDS-related opportunistic infections. There is no evidence that herpes zoster heralds the onset of an underlying malignancy. Race may influence susceptibility to herpes zoster. Blacks are one fourth as likely as whites to develop this condition. Although herpes zoster is not as contagious as the primary varicella infection, persons with reactivated infection can transmit varicella-zoster virus to nonimmune contacts. Household transmission rates have been noted to be approximately 15 percent. About 20 percent of patients with herpes zoster develop postherpetic neuralgia. The most established risk factor is age; this complication occurs nearly 15 times more often in patients more than 50 years of age. Other possible risk factors for the development of postherpetic neuralgia are ophthalmic zoster, a history of prodromal pain before the appearance of skin lesions and an immunocompromised state. Pathophysiology Varicella-zoster virus is a highly contagious DNA virus. Varicella represents the primary infection in the nonimmune or incompletely immune person. During the primary infection, the virus gains entry into the sensory dorsal root ganglia. How the virus enters the sensory dorsal root ganglia and whether it resides in neurons or supporting cells are not completely understood. The varicella-zoster virus genome has been identified in the trigeminal ganglia of nearly all seropositive patients. The virus remains latent for decades because of varicella-zoster virus­specific cell-mediated immunity acquired during the primary infection, as well as endogenous and exogenous boosting of the immune system periodically throughout life.8 Reactivation of the virus occurs following a decrease in virus-specific cell-mediated immunity. The reactivated virus travels down the sensory nerve and is the cause for the dermatomal distribution of pain and skin lesions. The pathophysiology of postherpetic neuralgia remains unclear. However, pathologic studies have demonstrated damage to the sensory nerves, the sensory dorsal root ganglia and the dorsal horns of the spinal cord in patients with this condition.

LABORATORY FINDINGS

CSF

• Cell count up to 300 lymphocytes/ul
• Protein 20 mg/dl - 110 mg/dl

• Intranuclear inclusions in skin cells or in multinucleated giant cells
• Immunofluorescent identification of the virus

LABORATORY FINDINGS

CSF

• Cell count 25/ul - 500/ul at first, mostly neutrophils;  after several days, lymphocytes predominate
• Protein normal at first;  50 mg/dl - 200 mg/dl within 2 weeks; normal by 6th week
• Glucose normal

• Leukocytosis (<15,000/ul) within 1st week
• Viral serologic tests show a fourfold increase in the titre of neutralising antibody from acute to convalescent sera.

LABORATORY FINDINGS

CSF

• Increased y-globulin, especially IgG
• Slight increase in lymphocytes
• Moderate increase in protein
• Increased measles antibody titre in subacute sclerosing panencephalitis
• Increased rubella antibody titre in progessive rubella panencephalitis
• Normal CSF in progressive multifocal leukoencephalopathy

• Increased measles antibody titre in subacute sclerosing panencephalitis
• Increased rubella antibody titre in progressive rubella panencephalitis

• Brain biopsy is required for a definitive diagnosis of progressive multifocal leukoencephalopathy.

LABORATORY FINDINGS

Serologic Tests for Syphilis

• Positive serum FTA-ABS test (95%) and VDRL test (75%) - negative VDRL usually occurs in late neurosyphilis
• Positive CSF VDRL test (25% - 82%) - this is highly specific for neurosyphilis but not very sensitive.  Positive CSF VDRL test with a positive serum FTA-ABS is diagnostic of neurosyphilis.  There are no standard procedures for the FTA-ABS test on spinal fluid.

• Normal findings (30%)
• Active disease
• WBC 200/ul-300/ul, mostly lymphocytes
• Preotein 40 mg/dl-200 mg/dl
• Increased y-globulin.
• Normal glucose

LABORATORY FINDINGS
 

• Leukocytosis
• Culture of abscess-the most common organism is Staphylococcus aureus; other organisms include streptococci, gram-negative bacilli, anaerobes

• WBC 20/ul - 100/ul
• Protein 100 mg/dl-400 mg/dl
• Glucose normal
• Cultures normal

• Vertebral osteomyelitis
• Bacteremia due to dental, respiratory, or skin infections or abscesses at other sites
• Diabetes mellitis

LABORATORY FINDINGS

• Leukocytosis 20,000/ul - 40,000/ul
• Cultures of empyema - in about half the cases, no organisms can be cultured or seen on Gram's stain.  Nonhaemolytic streptococci are the most common organisms when the preceding condition is sinusitis.  Staphylococcus aureus or gram-negative organisms are usually recovered following trauma or surgery.

• WBC 50/ul - 1000/ul; 20% - 80% neutrophils
• Protein 75 mg/dl - 300 mg/dl
• Normal glucose
• Cultures negative

Click on image for link to original image and information

B. EPIDURAL AND SUBDURAL ABSCESS OR EMPYEMA 1. Definitions: Abscesses are localized collections of pus. Pyogenic organisms are the infectious agent involved with abscess formation. Empyema describes the accumulation of pus within a space or cavity, again, typically secondary to pyogenic organism infection. Epidural and subdural infections can be called either abscess or empyema 2. Pathogenesis of Subdural Abscess/Empyema: a. Direct inoculation secondary to trauma, usually of organisms resident in the sinuses (often pneumococcus). b. Secondary to middle ear infections; organisms may erode directly into either space or spread via venous sinuses. 3. Etiologic agents: Usually bacteria; streptococcus and staphylococcus are the most common. 4. Pathological changes: Acutely a purulent exudate; organization later; reactive leptomeningitis; cerebral veins in the subdural space may be affected. 5. Spinal fluid changes: Reactive meningitis occurs; CSF changes include elevation of protein levels, PMN count, and sometimes pressure. No organisms can be cultured, unless the empyema is accompanied by infection of leptomeninges. 6. Complications: Space-occupying effects plus edema of brain may lead to herniation and midline shift. Infection may spread into leptomeninges and contaminate cerebrospinal fluid in subarachnoid space.

LABORATORY FINDINGS

• Leukocytes are normal or increased up to 15,000/ul
• Increased sedimentation rate
• If the subarachnoid space becomes involved by extension of the abscess to the surface of the brain or to the ventricles, then the CSF findings will be those of bacterial meningitis with grossly purulent spinal fluid and WBC > 50,000/ul
• In recent years, cultures of brain abscesses have shown increased isolation of obligate anaerobes especially Bacteroides species.  Anaerobic streptococci are also frequently isolated.  These organisms usually originate in the lung.  Enteric organisms are almost always associated with ear infections, and staphylococcal abscess commonly follows penetrating head trauma or bacteremia.

• WBC 20/ul - 300/ul;  10% - 80% neutrophils
• Protein 100 mg/dl
• Glucose normal
• Culture negative

• Lung abscess, pleural empyema, bronchiectasis infective endocarditis

Click on Image for link to original image and article

Brain Abscess: This photomicrograph shows the early capsule formation around an abscess, several weeks after the infection started. The blue aniline stain demonstrates the collagen which is being produced by fibroblasts derived from newly formed blood vessels. The cavity of the abscess is located towards the right upper corner. Some inflammatory debris is still accumulated on the surface. The surrounding brain tissue is edematous.

LABORATORY FINDINGS

• Leukocytosis
• Positive blood culture in about 50% of cases
• CSF - usually normal, but may show 10 WBC/ul - 4000 WBC/ul and slightly increased protein

LABORATORY FINDINGS

• Markedly increased serum ammonia;  increased serum glutamic-oxaloacetic transaminase (SGOT) (AST {aspartate aminotransferase}), serum glutamic-pyruvic transaminase (SGPT) (ALT {alanine aminotransferase}), amino acids, fatty acids, and LDH reflect hepatic injury
• Increased blood urea nitrogen (BUN) and creatinine reflect renal injury.
• Increased lactic acid, decreased bicarbonate, decreased pH (metabolic acidosis) due to impaired oxidative metabolism
• Later there is often decreased PCO2 and increased pH (respiratory alkalosis) - increased ammonia leads to hyperventilation
• Decreased blood glucose, sodium, potassium
• Prolonged prothrombin time reflects severe hepatic damage.
• Normal serum bilirubin
• Increased serum creatinine phosphokinase (CPK), especially MM* (muscle) fraction, occurs in severely affected children.  Progressive increase indicates a poor prognosis.
• CSF glucose is decreased in proportion with the decreased blood glucose level.

MULTIPLE SCLEROSIS

top NINDS Multiple Sclerosis Information Page
What is Multiple Sclerosis?
Multiple sclerosis (MS) is a life-long chronic disease diagnosed primarily in young adults. During an MS attack, inflammation occurs in areas of the white matter of the central nervous system (nerve fibers that are the site of MS lesions) in random patches called plaques. This process is followed by destruction of myelin, which insulates nerve cell fibers in the brain and spinal cord. Myelin facilitates the smooth, high-speed transmission of electrochemical messages between the brain, the spinal cord, and the rest of the body. Symptoms of MS may be mild or severe and of long duration or short and appear in various combinations. The initial symptom of MS is often blurred or double vision, red-green color distortion, or even blindness in one eye. Most MS patients experience muscle weakness in their extremities and difficulty with coordination and balance. Most people with MS also exhibit paresthesias, transitory abnormal sensory feeling such as numbness or "pins and needles." Some may experience pain or loss of feeling. About half of people with MS experience cognitive impairments such as difficulties with concentration, attention, memory, and judgment. Such impairments are usually mild, rarely disabling, and intellectual and language abilities are generally spared. Heat may cause temporary worsening of many MS symptoms. Physicians use a neurological examination and take a medical history when they suspect MS. Imaging technologies such as MRI, which provides an anatomical picture of lesions, and MRS (magnetic resonance spectroscopy), which yields information about the biochemistry of the brain. Physicians also may study patients' cerebrospinal fluid and an antibody called immunoglobulin G. No single test unequivocally detects MS. A number of other diseases produce symptoms similar to those seen in MS.

Is there any treatment?
There is as yet no cure for MS. Until recently, steroids were the principal medications for MS. While steroids cannot affect the course of MS over time, they can reduce the duration and severity of attacks in some patients. The FDA has recently approved new drugs to treat MS. The goals of therapy are threefold: to improve recovery from attacks, to prevent or lessen the number of relapses, and to halt disease progression.

What is the prognosis?
The cause of MS remains elusive, but most people with MS have a normal life expectancy. The vast majority of MS patients are mildly affected, but in the worst cases, MS can render a person unable to write, speak, or walk.

What research is being done?
Scientists are looking into the body's autoimmune system, infectious agents, and genetics as culprits in MS. Studies into these areas strengthen the theory that MS is the result of a number of factors rather than a single gene or other agent. Studies use a technique called magnetic resonance imaging (MRI) to visualize the evolution of MS lesions in the white matter of the brain. Studies have shown that MS has no adverse effects on the course of pregnancy, labor, or delivery; in fact, the stabilization or remission of symptoms during pregnancy may be attributable to changes in a woman's immune system that allows her to carry a baby.

LABORATORY FINDINGS

Increased CSF IgG index (>0.65) = CSF IgG/CSF albumin
                                                      Serum IgG/Serum albumin

• The IgG index is reported to have a higher degree of sensitivity and specificity than have other laboratory tests for multiple sclerosis when cerebral infections and immunologic diseases are eliminated.
• Increased CSF IgG and IgG/total protein ratio (about 67% of patients)
• Multiple discrete (oligoclonal) bands of CSF y-globulins are seen when using high-resolution agarose gel electrophoresis (85% - 95% of patients)
• Slight increase in CSF mononuclear cells (>50/ul) - in 25% of patients during an acute episode;  this reflects activity of the disease
• Slight increase in CSF protein (<100 mg/dl) - in 25% of patients
• Presence of myelin basic protein in CSF reflects fragments of myelin sheaths in the spinal fluid, indicating recent demyelination or acute disease activity

LABORATORY FINDINGS
 

• Idiopathic epilepsy and many cases of seizures of known origin - no abnormal laboratory findings
• Serum anticonvulsant levels are often necessary for optimal management of epileptic seizures and for the diagnosis of recurrent seizures.
• Common antiepileptic drugs, which may require blood-level monitoring, include phenobarbital, phenytoin, carbamazepine, primidone, ethosuximide, methsuximide, diazepam, valproic acid, and clonazepam.

• Hypoglycaemia (see Chap. 6)
• Meningitis*
• Encephalitis*
• Cerebral infarction*
• Cerebral haemorrhage*
• Brain tumour*
• Multiple sclerosis*
• Sickle cell anaemia
• Leukaemia
• Phenylketonuria
• Von Gierke's disease
• Porphyria

CEREBRAL INFARCTION

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LABORATORY FINDINGS

Cerebral Thrombosis

• CSF usually entirely normal
• CSF protein might be increased up to 50 mg/dl - 80 mg/dl
• CSF WBC might be increased up to 50/ul during first 48 hours;  rarely there is a transient increase to 400/ul - 2,000 about the third day.
• Increased serum CPK (50% of patients) - appears after 2 days, peaks at 3 days, returns to normal by 14 days
• Increased serum SGOT (AST) (50% of patients) - appears after 7 days

• Usually the same as in cerebral thrombosis
• Up to 65% of patients show slight xanthochromia - reflects the occurrence of haemorrhagic infarction
• Rarely, a patient with a haemorrhagic infarct might show up to 10,000 RBC/ul.

LABORATORY FINDINGS

Epidural and Subdural Haemorrhage

• Usually no CSF findings unless blood enters the subarchnoic space

• Occult blood may be present in CSF within 8 hours after symptoms.
• Haemoglobin may persist in CSF for 8 days.
• Xanthochromia, due primarily to bilirubin, appears after 8 hr - 12 hr and persists for 20 days - 30 days.
• Gross blood is present in CSF in 85% of patients;  blood usually does not clot and is uniform in all tubes;  blood clears by the 10th day in 40% of patients.
• WBC - RBC ratio in bloody spinal fluid is usually the same as in peripheral blood.  However, it may be higher than in peripheral blood because of an accompanying inflammatory reaction in the meninges.
• Increased CSF protein (up to 1000 mg/dl)
• Transient albuminuria and glycosuria
• Leukocytosis of 15,000/ul - 18,000/ul
• Increased sedimentation rate

• Laboratory findings are similar to those in subarachnoid haemorrhage only if and when blood enters the ventricles or subarachnoid space.

LABORATORY FINDINGS

CSF

• The following findings occur only when products of tumour necrosis or malignant cells gain access to the CSF through the subarachnoid space or ventricles:
• Appearance usually clear, occasionally xanthochromic
• WBC up to 150/ul (25% of patients)
• Increased protein, up to 500 mg/dl
• Tumour cells may be present on cytologic examination.
• Glucose may be decreased if tumour cells are present.

• Anterior pituitary insufficiency
• Diabetes insipidus
• Hypothyroidism
• Secondary testicular failure
• Secondary ovarian failure
• Precocious puberty

• Bronchogenic carcinoma (see Chap. 2)
• Leukaemia (see Chap. 8)
• Malignant lymphoma (see Chap. 8)

top What are Brain and Spinal Tumors?
Brain and spinal cord tumors are abnormal growths of tissue found inside the skull or the bony spinal column, which are the primary components of the central nervous system (CNS). Benign tumors are noncancerous, and malignant tumors are cancerous. The CNS is housed within rigid, bony quarters (i.e., the skull and spinal column), so any abnormal growth, whether benign or malignant, can place pressure on sensitive tissues and impair function. Tumors that originate in the brain or spinal cord are called primary tumors. Most primary tumors are caused by out-of-control growth among cells that surround and support neurons. In a small number of individuals, primary tumors may result from specific genetic disease (e.g., neurofibromatosis, tuberous sclerosis) or from exposure to radiation or cancer-causing chemicals. The cause of most primary tumors remains a mystery. They are not contagious and, at this time, not preventable. Symptoms of brain tumors include headaches, seizures, nausea and vomiting, vision or hearing problems, behavioral and cognitive problems, motor problems, and balance problems. Spinal cord tumor symptoms include pain, sensory changes, and motor problems. The first test to diagnose brain and spinal column tumors is a neurological examination. Special imaging techniques (computed tomography, and magnetic resonance imaging, positron emission tomography) are also employed. Laboratory tests include the EEG and the spinal tap. A biopsy, a surgical procedure in which a sample of tissue is taken from a suspected tumor, helps doctors diagnose the type of tumor.

Is there any treatment?
The three most commonly used treatments are surgery, radiation, and chemotherapy. Doctors also may prescribe steroids to reduce the swelling inside the CNS.

What is the prognosis?
Symptoms of brain and spinal cord tumors generally develop slowly and worsen over time unless they are treated. The tumor may be classified as benign or malignant and given a numbered score that reflects how malignant it is. This score can help doctors determine how to treat the tumor and predict the likely outcome, or prognosis, for the patient.

LABORATORY FINDINGS

CSF

• Protein 50 mg/dl - 3500 mg/dl (85% of patients);  when protein is high, CSF usually clots because of the presence of increased fibrinogen
• Xanthochromia (40% of patients)
• WBC 25/ul - 100/ul (15% of patients)
• Glucose normal

Nodular tumor within spinal cord with surrounding cyst

After resection of tumor nodule-Click on images or for link to source document

LABORATORY FINDINGS

• Early leukocytosis

• Increased protein (50 mg/dl - 100 mg/dl) - this reflects the widespread inflammation of the nerve roots;  the protein increase usually begins after the 10th day of the neurologic illness and peaks at 4 wk-6wk;  the increase parallels the clinical severity
• Normal cell count (90% of patients);  slightly increased mononuclear cells (10% of patients)

LABORATORY FINDINGS

• Increased serum CPK;  MM**(muscle) band seen on electrophoresis
• Increased serum aldolase
• Myoglobinuria and acute renal failure might occur.
• Frequent macrocytosis and decreased RBC folate result from increased alcoholic intake
• Increased y-glutamyl transpeptidase indicates increased alcoholic intake.
*The combination of increasd CSF protein with the usually normal CSF cellularity is referred to as albuminocytologic dissociation.
**See definition

MYASTHENIA GRAVIS

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Myasthenia gravis is the most common primary disorder of neuromuscular transmission. The disorder typically strikes between the ages of 20 and 50, with women developing symptoms younger and men developing symptoms later.  Unlike many other neurological disorders, myasthenia gravis does not cause progressive muscle atrophy (wasting away or degeneration).  The disorder can be caused by an acquired immunologic abnormality or by a genetic abnormality.

Symptoms

Initially, people with myasthenia gravis may complain about specific muscle weakness, particularly in the eyes, face and neck.  They may have difficulty swallowing, chewing or speaking, and may have double vision. They also may feel fatigue, especially later in the day. Symptoms can be aggravated by emotional stress, systemic illness such as a viral respiratory infection, menstrual cycle, pregnancy, hypothyroidism or hyperthyroidism, and other factors.

LABORATORY FINDINGS

• Presence of serum antibodies to acetylcholine receptors (87% - 93% of patients) - this is the best diagnostic test;  the antibody titre does not correspond with the severity of the disease or with the response to therapy
• Normal CPK, aldolase, SGOT (AST) and LDH

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MUSCULAR DYSTROPHIES

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LABORATORY FINDINGS
 

• Increased serum CPK, aldolase, SGOT (AST), and LDH reflect skeletal-muscle breakdown and the release of enzymes from muscle into serum.  The serum level reflects the severity of muscle damage.  CPK isoenzymes include both MM* and MB*.  There is increased MB* isoenzyme in diseased skeletal muscle.  he increased LDH isoenzyme is usually LDH5.
• A recent detailed study demonstrated the following findings in Duchenne's muscular dystrophy:6

Early:  Moderate increase in LDH4, marked increase in LDH5
Progressing:  Moderate increases in LDH4 and LDH5
Late:  Moderate increases in LDH3 and LDH4; normal LDH5

• This may be interpreted as indicating a gradual disappearance of degenerating mature muscle fibres (LDH5) and an increased synthesis of immature muscle fibres (LDH1 - LDH3) as regeneration occurred.

Click on Image for link to MD page

Muscular Dystrophies and Myopathies Myopathies are diseases of the muscles.  They can be caused by an inherited genetic abnormality (as in muscular dystrophy) or an abnormality of the immune system (such as polymyositis).  These disorders can develop at any time from birth through adulthood.  University of Chicago neurologists have expertise in treating many different muscle diseases. There are many types of muscular dystrophy (MD). These diseases are classified according to the muscle groups involved and the age of onset.  Some of these muscular dystrophies result in premature death; others may allow the person to live for decades with varying degrees of disability. Symptoms  Muscular dystrophy is characterized by muscle weakness in various parts of the body, depending on the type of MD or myopathy.  Muscle weakness progresses (worsens) over time.  Initial symptoms usually develop gradually.

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FAMILIAL PERIODIC PARALYSIS


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Familial periodic paralysis

Alternative names:

hypokalemic periodic paralysis; periodic paralysis - familial; periodic paralysis - hypokalemic

Definition:

A disorder that occurs within certain families and causes intermittent episodes of >muscle weakness

Causes, incidence, and risk factors:

Familial periodic paralysis is a condition of intermittent episodes ofparalysis or muscle weakness that occurs in multiple members of a family group. Many (but not all) cases of familial periodic paralysis are termed "hypokalemic" periodic paralysis.

Hypokalemic periodic paralysis occurs as an inherited condition. In most cases, it is inherited as an autosomal dominant disorder (only one parent must transmit the gene). In other cases, the disorder appears sporadically in a family group.

The disorder involves attacks of muscle weakness or paralysis alternating with periods of normal muscle function. Attacks usually begin in adolescence but can occur before age 10. Attacks of intermittent weakness that do not begin until adulthood are rare and usually caused by other disorders. The frequency of attacks varies from daily to yearly. Episodes of muscle weakness may last for a few hours or persist for several days.

During an attack of muscle weakness, there is a low level of potassium in the bloodstream (serum). Serum potassium levels are normal between attacks. There is no decrease in total body potassium, however. Potassium flows from the bloodstream into muscle cells. Insulin levels may affect the disorder in some people because insulin increases the flow of potassium into cells.

Weakness most commonly affects the muscles of the arms and legs but may occasionally affect the eye muscles or the muscles involved in breathing and swallowing (which can be fatal). Although muscle strength is initially normal between attacks, repeated attacks may eventually cause progressive and persistent muscle weakness between attacks.

Risks include a family history of periodic paralysis. Attacks may be triggered by ingestion of high carbohydrate meals. Attacks most commonly occur after sleep or rest and are rare during exercise, but rest after an exercise period may trigger an attack. The risk is slightly higher in Asian men who also have thyroid disorders thyrotoxic periodic paralysis.

Disorders that cause intermittent episodes of paralysis as their primary effect are uncommon. Familial periodic paralysis occurs in approximately 1 out of 100,000 people. Men are affected more often than women and usually have more severe symptoms.

LABORATORY FINDINGS
 

• Decreased serum potassium (2.5 mEq/l - 3.5 mEq/l) - hypokalemic type
• Increased serum potassium (5.0 mEq/l - 7.0 mEq/l) - hyperkalemic type
• Serum potassium is usually normal between attacks.
• Increased CPK during acute attacks.

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