AM2 Neurology

I.          Meningitis and Encephalitis

            1.      Identify Streptococcus pneumoniae and Neisseria meningitidis as the two most common causes of acute bacterial meningitis in adults.

Jenn, CMDT pp1351 &1367

Streptococcus pneumoniae is the most common cause of meningitis in adults and the second most common cause of meningitis in children over the age of 6 years. Head trauma, cerebrospinal fluid leaks, and sinusitis may precede it.

Meningococcal meningitis is caused by Neisseria meningitidis of groups A, B, C, Y, W-135, and others. Meningitis due to serogroup A is uncommon in the United States. Serogroup B generally causes sporadic cases. The frequency of outbreaks of meningitis caused by group C meningococcus has increased in recent years, and this serotype is the most common cause of epidemic disease in the United States. Up to 40% of persons are nasopharyngeal carriers of meningococci, but relatively few develop disease. Infection is transmitted by droplets. The clinical illness may take the form of meningococcemia (a fulminant form of septicemia without meningitis), meningococcemia with meningitis, or predominantly meningitis. Chronic recurrent meningococcemia with fever, rash, and arthritis can occur, particular in those with terminal complement deficiencies.

(Jenn, Noble pp1551)

The most common organisms responsible for bacterial meningitis in people over the age of 2 months are Neisseria meningitidis, Streptococcus pneumoniae, Haemophilus influenzae, and Listeria monocytogenes, but other organisms such as Escherichia coli and group B streptococci must be considered in neonates.

Megan Noble 1551

The most common organisms responsible for bacterial meningitis in people over 2 months are Nesseria menengitidis and Streptococcus pneumoniae.

Dustin, CMDT pg. 1351, 1367

Streptococcus pneumoniae is the most common cause of meningitis in adults.

Meningococcal meningitis is caused by Neisseria meningitides of groups A, B, C, Y, W-135, and others.  Meningitis due to serogroup A is uncommon in the U.S.  Serogroup B generally causes sporadic cases.  The frequency of outbreaks of meningitis caused by group C meningococcus has increased in recent years, and this serotype is the most common cause of epidemic disease in the U.S.

Anonymous Current p. 1253, Table 30-1.

Strep pneumo and N. meningitidis are the two most common microorganisms causing pneumonia in those 18-50 years of age.

Anonymous Nobel pg 1551

The most common organisms responsible for bacterial meningitis in people over the age of 2 months are Neisseria meningitis, Streptococcus pneumoniae, H. flu, & Listeria moncytogenes, but other organisms like E. Coli and B strep must be considered in neonates.   

Anonymous  Noble 1554

Neisseria Meningitis has a prevalence of 30-40% in adult cases and Strep pneumoniae has a prevalence of about 40-50%.  

            2.      Describe or recognize the classic clinical picture seen in a patient with acute bacterial meningitis.

Jenn, Noble pp1552

Acute Bacterial Meningitis

Clinical Features.

Acute meningitis evolves over hours or, at most, days. Patients who have been quite healthy or have only had an upper respiratory infection now begin to complain of the symptoms of meningeal irritation and of raised intracranial pressure (ICP). Malaise; fever; headaches of traction type; nausea; vomiting; anorexia; stiff, painful neck; and photophobia are the usual initial symptoms. Depression in the level of consciousness, delirium, seizures, and various focal neurologic signs may follow. The association of fever and any form of mental deterioration must make one consider meningoencephalitis as a possible diagnosis. Inflammatory cells in the CSF and accompanying cerebral edema may cause a rapid rise in ICP and produce false localizing signs.

Examination usually shows meningism, with stiff neck and resistance to flexion of the spine or to straight leg raising. Such signs may be absent in overwhelmingly ill adults and in neonates, who may just show the features listed in Box 165-2 , such as a bulging fontanelle, neck stiffness, and drowsiness. Children may also show head retraction, which can be so marked as to warrant the term opisthotonos.

General examination may show a rash (particularly if the meningococcus is involved or echovirus or coxsackievirus is involved); signs of infection in the ears, joints, bones, chest, or heart; and sometimes purpura and hypotension. Shock is common if a gram-negative organism is the cause of septicemia with secondary meningitis and in meningococcal septicemia causing adrenal infarction (WaterhouseFriderichsen syndrome). The combination of fever and purpura in this context can occur with N. meningitidis, echovirus, E. coli, Pseudomonas, Proteus, L. monocytogenes, streptococcus, gonococcus, or Staphylococcus aureus infections.

Megan Noble 1552

Acute meningitis evolves over hours or at most days.  Patients who have been white healthy or have only had an upper respiratory infection now begin to complain of the symptoms of meningeal irritation and of raise intracranila pressure (ICP).  Malaise, fever, headaches of traction type, nausea, vomiting, anorexia, stiff, painful neck and photophobia area the usual initial symptoms.  Depression in the level of consciousness, delirium, seizures and various focal neurologic signs may follow.  The association of fever and any form of mental deterioration must make one consider meningoencephalitis as a possible diagnosis.

Dustin, Noble online

Acute meningitis evolves over hours or, at most, days.  Patients who have been quite healthy or have only had an upper respiratory infection now begin to complain of the symptoms of meningeal irritation and of raised intracranial pressure (ICP).  Malaise; fever; headaches of traction type; nausea; vomiting; anorexia; stiff, painful neck; and photophobia are the usual initial symptoms.  Depression in the level of consciousness, delirium, seizures, and various focal neurologic signs may follow.  The association of fever and any form of mental deterioration must make one consider meningoencephalitis as a possible diagnosis.

Anonymous Current p. 1253

A. Purulent Meningitis.

Presentation: acutely within hours or 1-2 days after onset of symptoms. 

Responsible organisms: Strep pneumo and N. meningiditis in 18-50 year olds.

Anonymous  Noble 1152

Acute meningitis evolves over hours, or at most, days.  Patients who have been quite healthy or have only had an upper respiratory infection begin complaining of meningeal irritation and of increased intracranial pressure.

•        Malaise

•        Fever

•        Headaches of traction type

•        Nausea and vomiting

•        Anorexia

•        Stiff, painful neck

•        Photophobia

•        Depressed LOC, delirium, seizures, and focal neurological signs may follow

Examination usually shows meningism, with a stiff neck and resistance to flexion of the spine or to straight leg raises.  Such signs may be absent in overwhelmingly ill adults and in neonates.  Neonates and older infants may present with a bulging fontanelle, neck stiffness, and drowsiness. General examination may show a rash (particularly if the meningococcus is involved or echovirus or coxsackievirus is involved); signs of infection in the ears, joints, bones, chest, or heart; and sometimes purpura and hypotension.  Shock is common if a gram-negative organism is the cause with secondary meningitis and in meningococcal septicemia causing adrenal infarction.

Anonymous   Noble, p.1552

Malaise, fever, headaches of traction type, nausea, vomiting, anorexia, stiff painful neck, and photophobia. Progressive sx include depression in level of consciousness, delirium, seizures, and various focal neurologic signs. Bulging fontanelles in kids under 2.

            3.      Describe or recognize the typical CSF findings seen in acute bacterial meningitis; identify the WBC with differential and blood cultures as important additional studies to be obtained.

Jenn, Noble pp1552

Evaluating the Cerebrospinal Fluid.

Whenever there is evidence of meningeal inflammation, a lumbar puncture (LP) must be done eventually, even though some patients with meningitis show early papilledema.

The fluid may be turbid or clear; microscopy may show any number of mononuclear or polymorphonuclear cells. PMNs almost always predominate in acute bacterial meningitis. Mononuclear cells usually predominate in the other forms of meningitis (due to Mycobacterium tuberculosis, viruses, or fungi).

Megan Noble 1552-1553

Whenever there is evidence of meningeal inflammation a lumbar puncture must be done.  

               CSF protein levels are raised in all forms of meningitis, particularly those of longer duration or with very high cell counts.  The technology of DNA amplification and PCR can identify the causative agent within 30 minutes.The CSF blood sugar levels are normal with viral meningitis, values are low ( <50% of blood level) in bacterial meningitis.  High PMN counts are to be expected in all cases->50,000/mm³ if the meningitis is due to rupture of an abscess.

               If there is clinical uncetainity as to whether the patient has bacterial or aseptic meningitis and the patient is not seriously ill, the physician may properly maintain careful observation and repeat the LP in 12-18 hours.  With aseptic meningitis, the second CSF sample will almost always show a shift toward mononuclear cell predominance, whereas later examinations will show the eventual disappearance of all PMNs.  In bacterial meningitis, PMNs increase quickly, CSF sugar fall and the protein level rises.

            Blood cultures should be obtained and any skin lesions swabbed before the antibiotic is started.

Anonymous CMDT 1252

Central Nervous system infection constitutes a medical emergency.  Immediate diagnostic steps must be instituted to establish the specific cause.  Normally these include the history, PE, blood count, blood culture, LP, and a chest film.

Dustin, Noble online.

The CSF pressure need not be taken if the initial fluid is cloudy or bloodstained because knowledge of the pressure does not contribute to diagnosis in these circumstances. The fluid may be turbid or clear; microscopy may show any number of mononuclear or polymorphonuclear cells. PMNs almost always predominate in acute bacterial meningitis. Mononuclear cells usually predominate in the other forms of meningitis (due to Mycobacterium tuberculosis, viruses, or fungi).

CSF protein levels are raised in all forms of meningitis, particularly those of longer duration or with very high cell counts.

If there is clinical uncertainty as to whether the patient has bacterial or aseptic meningitis and the patient is not seriously ill, the physician may properly maintain careful observation, withhold antibiotics, and repeat the LP in 12 to 18 hours. With aseptic meningitis, the second CSF sample will almost always show a shift toward mononuclear cell predominance, whereas later examinations will show the eventual disappearance of all PMNs. In bacterial meningitis, PMNs increase quickly, CSF sugar falls, and the protein level rises.

The LP in Meningococcal meningitis typically reveals a cloudy or purulent CSF, with elevated pressure, increased protein, and decreased glucose content.  The fluid usually contains more than 1000 cells/uL, with polymorphonuclear cells predominating and containing gram-negative intracellular diplococci.  (CMDT pg. 1367)

The CSF in pneumococcal meningitis typically has more than 1000 white blood cells per microliter, over 60% of which are polymorphonuclear leukocytes; the glucose concentration is less than 40 mg/dL, or less than 50% of the simultaneous serum concentration; the proteinusually exeeds 150 mg/dL. (CMDT 1351)

Current p. 1253, Table 30-2.

Typical CSF findings in purulent meningitis (bacterial) community acquired:

-200-20,000 polymorphonuclear neutrophils (PMNs)

-Low glucose (<45)

-High protein (>50)

-Opening pressure markedly elevated

Anonymous  Noble 1552

The fluid may be cloudy; microscopy may show polymorphonuclear cells.  PMN’s almost always predominate in acute bacterial meningitis.  CSF protein levels are raised in all forms of meningitis.  A simultaneous estimation of the CSF blood sugar is mandatory when the LP is done.  CSF sugar values will be less than 50% of the blood level in bacterial meningitis.

(Tininalli 1486) A blood culture is mandatory in all cases of meningitis.  Blood cultures (two specimens drawn 15 minutes apart) yield the responsible organism in about 50% of cases of bacterial meningitis, but CSF analysis is paramount.  A WBC with differential is an important additional study.

Anonymous Noble pp. 1552-1555

The fluid may be turbid or clear; microscopy may show any # of mononuclear or PMN cells. PMNs almost always predominate in ABM while mononuclear cells predominate in other types. High PMNs are to be expected in all cases - over 50,000/mm³ if the meningitis is due to rupture of an abscess. Protein levels are raised in all forms of meningitis, particularly with high cell counts or long duration. CSF blood sugar estimations are mandatory when the LP is done – values will be low (< 50% of the blood level) in bacterial meningitis.

In ABM, PMNs increase quickly, CSF sugar falls, and the protein level rises.

Hold the CSF up to the light to see if it is cloudy (over 500 cells/ml) or clear, and then take it to the lab, where a Gram’s stain, culture, cell count, and differential should be performed and the protein and sugar levels estimated. Virus cultures and cytology might be indicated if septic meningitis is excluded by these tests. In some cases (endocarditis, prior head trauma) the CSF may not show many leukocytes and may be sterile. A blood culture is mandatory in all cases of meningitis so the correct diagnosis should not be missed.

            4.      Describe the importance of obtaining CT scan, when possible, prior to lumbar puncture if there is any suspicion of a space-occupying lesion.

Jenn, Noble pp1552

Intracerebral abscess or expanding mass lesions, particularly in the posterior fossa, must be ruled out by physical examination, although in the presence of any focal signs an emergency computed tomography (CT) scan is necessary. In this situation an expert opinion should be requested if available.  LP should be performed when any such masses are excluded because identification of the organism and determination of its sensitivities are essential; however, if a bacterial process is suspected, antibiotics should be started as soon as blood cultures are drawn and before an LP is done.

Megan CMDT 1252

Since performing a lumbar puncture in the presence of a space-occupying lesion ( brain abscess, subdural hematoma, subdural abscess) can result in brain stem herniation and death, a CT scan is performed prior to LP if a space occupying lesion is suspected on the basis of papilledema, coma, seizures, or focal neurologic findings.

Dustin, Noble online.

Whenever there is evidence of meningeal inflammation, a lumbar puncture (LP) must be done eventually, even though some patients with meningitis show early papilledema. Intracerebral abscess or expanding mass lesions, particularly in the posterior fossa, must be ruled out by physical examination, although in the presence of any focal signs an emergency computed tomography (CT) scan is necessary. In this situation an expert opinion should be requested if available. LP should be performed when any such masses are excluded because identification of the organism and determination of its sensitivities are essential; however, if a bacterial process is suspected, antibiotics should be started as soon as blood cultures are drawn and before an LP is done.

Anonymous Current p. 1252.

The Answer:  Since performing a LP in the presence of a space-occupying lesion (brain abscess, subdural hematoma, subdural abscess) can result in brain stem herniation and death, a CT scan is performed prior to LP if a space-occupying lesion is suspected on the basis of papilledema, coma, seizures, or focal neurologic findings.

Additional Info:  If there is a delay in obtaining a CT scan and bacterial meningitis is suspected, blood cultures should be drawn and antibiotics should be administered even before CSF is obtained for culture to avoid treatment delay.  Studies suggest that antibiotics given within 4 hours before obtaining CSF will not affect culture results.

Anonymous   Tininalli 1487

A cranial CT scan should be done first if the patient exhibits papilledema or focal neurological signs.  If the differential includes parenchymal brain infections and mass lesions, a LP is potentially dangerous since it can lead to transtentorial or tonsillar herniation.  A CT scan is the preferred mode in diagnosing subarachnoid hemorrhage.

(Noble 1552) Whenever there is evidence of meningeal inflammation, a lumber puncture must be done eventually, even though some patients with meningitis show early papilledema.  A head CT scan may need to be done if a intracerebral abscess or expanding mass lesion is suspected first and expert opinion sought.  LP should be performed when any such masses are excluded because identification of the organism and determination of its sensitivities are essential; however, if a bacterial process is suspected, antibiotics should be started as soon as blood cultures are drawn and before an LP is done.

Anonymous Tintinalli, pg. 1425

Noncontrast CT scan can usually exclude critical lesions or mass effects of tumors with increased intracranial pressure (ICP).  Contraindications to Lumbar Puncture (LP include the suspicion of raised ICP, which can be excluded by the absence of papilledema, normal level of consciousness, and normal findings on neurological exam.

Venous pulsations seen at the disc margins on fundoscopic exam with the patient upright effectively rule out ICP.  Venous pulsations may be terminated temporarily with pressure on the globe.  If these conditions are met, then a CT scan need not necessarily be carried out prior to LP, especially if the CT is likely to be delayed.

            5.      Since antibiotic choices change rapidly, you will not be ask ed to learn  specific recommendations for this.  Be aware that you may have to make empiric antibiotic choices based on patient's age, clinical circumstances, etc., before a  definitive bacterial pathogen can be identified.

Anonymous Current p. 1252, Table 30-1.

-18 to 50: cefotaxime or cephtriaxone (for S. pneumo, N. meningitides)

-Over 50: ampicillin, cephotaxime or cephtriaxone (for same as above and L. monocytogenes, gram negative bacilli)

-Impaired cellular immunity: ampicillin plus ceftazidime (for L. monocytogenes, gram negative bacilli, S. pneumo)

-Post surgical or posttrauma: vancomycin plus cephtazidime (for S. aureus, S. pneumo, gram negative bacilli)

            6.      Identify the need for prophylaxis of close contacts of patients with meningitis caused by Neisseria meningitidis and Hemophilus influenzae type b.

Suzy Noble 1555

Rifampin, is used for prophylaxis should be used for all household contacts and others closely associated with patients suffering from meningococcal disease (eg.,children in the same nursery school). Vaccination against meningococcal is also available and is an important public health measure.

Shauna Noble 1555

Prophylaxis should be used for all household contacts and others closely associated with patients suffering from meningococcal disease (eg.,children in the same nursery school). Rifampin is the recommended treatment for prophylaxis. Vaccination against meningococcal is also available and is an important public health measure.

Anonymous Current p. 1368.

Household members exposed to a person with meningococcal meningitis are at increased risk and should be given rifampin prophylaxis.  Day care center contacts are treated in same manner.  School and work contacts need NOT be treated.  Hospital contacts need NOT be treated unless intense exposure has occurred (mouth to mouth).

Anonymous  Noble 1555

• Prophylaxis should be used for all household contacts and others associated with patients suffering from meningococcal disease.

• Rifampin 600 mg bid for 2 days for adults, and 10 mg/Kg bid in children, and in infants 3 months to 1 year 5 mg/Kg bid.

• Prophylaxis treatment is also recommended in contacts of cases of H. influenzae; rifampin is recommended at a dosage of 20 mg/Kg/day (not to exceed 600 mg/day).

Anonymous Noble says  pp. 1555 :

Prophylaxis should be used for all household contacts and others closely associated with patients suffering from meningococcal disease (e.g., children in the same nursery school).  They list Rifampin as drug of choice.

            7.      Describe or recognize the typical clinical syndrome of acute aseptic (viral) meningitis, including CSF findings.

Suzy Noble 1555, CMDT 1253

Fever, headache, and meningeal signs. Change in consciousness and localizing neurologic signs are rare. Patients look and feel wretched but are not severely ill. CSF examination will usually show an increase in mononuclear cells to fever than 500/mm³ (although PMNs may be increased in the early stages); the protein is normal or only slightly elevated, and the CSF sugar is usually normal, except with mumps infection.

Shauna Noble 1555

Characterized by fever, headache, and meningeal signs. Change in consciousness and localizing neurologic signs are rare. Patients with this disease look and feel wretched but are not severely ill. CSF examination will usually show an increase in mononuclear cells to  500/mm³ ; the protein is normal or only slightly elevated, and the CSF sugar is usually normal, except with mumps infection.

Anonymous Current p. 1253, Table 30-2.

Typical CSF findings in aseptic meningitis (viral):

-25 to 2,000 cells, mostly lymphocytes

-Normal or low glucose

-High protein (>50)

-Slightly elevated opening pressure

Anonymous  Noble 1555

• Acute aseptic meningitis is characterized by fever, headache, and meningeal signs. Change in consciousness and localizing neurologic signs are rare.

• CSF findings will usually show an increase in mononuclear cells to fewer than 500/mm3 , the protein is normal or slightly increased, and the glues level is usually normal, except with mumps infection.

Anonymous  Noble chap 165

Characterized by fever, HA and meningeal signs (irritability, drowsiness, possibly a stiff neck, vomiting). A change in consciousness and localizing signs are rare. Patients look and feel wretched, but are not severely ill. CSF exam will usually show an increase in mononuclear cells to fewer than 500/mm³. PMN’s may be increased in the early stages. Protein is normal or only slightly elevated, and the CSF sugar is usually normal, except with a mumps infection.

            8.      Describe the usual clinical course and lack of neurological sequelae seen in most cases of acute viral meningitis.

Suzy Noble 1555

Requires only analgesics and reduction in fever; the prognosis here is much better than in bacterial meningitis - the pt. is seldom as ill and usually recovers readily. An attempt to identify the virus by culture of the CSF or by PCR. A chest x-ray, tuberculosis skin test, syphilis serology, blood cultures, and a collagen-vascular screen are commonly ordered. CT scan to rule out a parameningeal focus.

Shauna Noble 1555, CMDT 1253

Known causes are common viral infections (coxsackievirus, echovirus, Epstein-Barr, mumps and lymphocytic choriomeningitis). Change in consciousness and localizing neurologic signs are rare.  Management requires only analgesics and reduction in fever. Prognosis is much better than in bacterial meningitis. It’s much more benign and is self limiting

Anonymous Current p. 1253.

Aseptic (viral) meningitis is much more benign and self limited than purulent meningitis.

Noble p. 1555.

Treatment requires only analgesics and fever reduction.  The patient is rarely ill and usually recovers readily.  Aseptic meningitis is characterized by fever, headache and meningeal signs.  Change in consciousness and localizing neurologic signs are rare.

Anonymous

• Most common causes of aseptic meningitis are viral infections; coxsackievirus, echovirus, Epstein-Barr virus, mumps, and the LCM virus.

• Management usually requires only analgesics and reduction in fever. The prognosis is much better than bacterial meningitis, the patient is seldom ill and usually recovers readily.

Anonymous  Noble, pg. 1555

-70% of the known causes of aseptic meningitis are common viral infections (coxsackievirus, echovirus, Eptein-Barr virus, mumps, and lymphocytic choriomeningitis [LCM]).  In about 25% of the cases the virus is not defined.  The remaining long list of viruses identified includes measles, chickenpox, and influenza.  Rarely, the clinical picture of aseptic meningitis may be seen in the preicteric stage of infectious hepatitis or in uremia and in patients with inadequately treated bacterial meningitis.

-Management of acute septic meningitis requires only analgesics and reduction in fever; the prognosis here is much better than in bacterial meningitis – the patient is seldom as ill and usually recovers readily.

            9.      Identify tuberculosis and fungi as common causes of subacute and chronic infectious meningitis.

Suzy Noble 671, 1555

Inadequately treated bacterial meningitis, fungal infections, and tuberculosis meningitis (TBM) are the more common causes of subacute meningitis.

            TBM-most likely to occur in native and immigrant populations, among alcoholics, and those with immunologic deficiency or generalized illness.

Shauna Noble 1555

Inadequately treated bacterial meningitis, fungal infections, and tuberculosis meningitis (TBM) are the more common causes of subacute meningitis; viral causes are much less common.

Anonymous Current p. 1253

B. Chronic Meningitis.

-Patients with chronic meningitis present less acutely with a history of symptoms lasting weeks to months. 

-The most common pathogens are:

Mycobacterium tuberculosis

fungi (cryptococcus for example)

atypical mycobacteria

spirochetes

Anonymous

Inadequately treated bacterial meningitis, fungal infections, and tuberculosis meningitis are the most common cause of subacute meningitis

Anonymous  Noble Ch. 165 p.

Subacute meningitis from these causes is much more common than viral causes. They are most likely to occur in North American native, immigrant, alcoholic + immunocompromised populations. About 1/3 of cases happen prior to 10y/o. Half of cases are from known TBM. Illness usually occurs in the active stage of primary infection, but can present years later.

Chronic meningitis is uncommon but caused by the same organism as subacute meningitis + is characterized by

            10.    Identify cryptococcal meningitis as a common cause of CNS infection in AIDS patients.

Suzy Noble 292, 1556

Cryptococcal meningitis has an insidious onset, with evidence of a confusional state, focal signs, and raised ICP. Although a smoldering meningitis is the usual presentation, abscesses may form. This condition occurs in those with immunologic deficiencies, AIDS, diabetes, or chronic alcoholism.

Shauna Noble 1556

Cryptococcal meningitis also has an insidious onset, with evidence of a confusional state, focal signs, and raised ICP. This condition occurs in those with immunologic deficiencies, AIDS, diabetes, or chronic alcoholism.

Anonymous Current, p. 972, 1487.

-Cryptococcus is the most common cause of fungal meningitis (overall – not just in AIDS patients).

-Factors that predispose patients to cryptococcal infections (all cryp. infecs., not just cryp. mening.) include HIV infection.

-Cryptococcal meningitis is a common opportunistic infection in AIDS patients.

Anonymous  Noble p. 1556  True  objective explains itself

A clinical point of interest in cryptococcal meningitis is prolonged and severe nature of the headache that precedes cranial nerve palsies, meningism, or increased ICP. Diagnosis is made with India ink-stained CSF preparations, but cryptococcal antigen should be detected in the blood and CSF.

Anonymous  Noble 1556

Cryptoccal meningitis has an insidious onset with evidence of a confusional state, focal signs, and raised ICP.  Although a smoldering meningitis is the usual presentation, abscesses may form.  This condition also occurs in those with immunologic deficiencies, AIDs diabetes or chronic alcoholism.  Patients with AIDS need long-term suppressive treatment with fluconazole.  

            11.    Describe or recognize the typical clinical syndrome of acute viral encephalitis.

Aprilt Current p. 1254

Encephalitis due to herpes, arbo, rabies and flaviviruses ( West Nile encephalitis, Japanese encephalitis ) and many other viruses produce disturbances in sensorium, seizures, and many other manifestations.  Patients present with more acutely and are more ill thatn patients with aseptic meningitis.  Cerebrospinal fluid may be entirely normal or may show lyphocytes.

            Aprilt Noble 2nd ed. p. 1369

Consists of a febrile illness with headache, vomiting, photopobia, and rapid  evolution wover a day or two of progressive stupor, convulsions, and a combination of upper motor neuron, cerebellar, and brainstem derangements.  The  CSF profile is similar to that of acute viral (aseptic) meningitis: reveals a leukocyte count <1000 with a predominance of mononuclear cells and a protein level <100.  Sugar and gram stain are normal.

Anonymous Noble p. 1557.

-Acute viral encephalitis involves infection of the brain parenchyma.

-HSV, enterovirus and arbovirus are common causative agents.

-Clinical features: fever, meningism, increased ICP signs, decreased LOC, generalized or focal seizures, other focal signs (dependent upon brain region affected).

-Consider encephalitis if you see: fever plus meningism with signs of cerebral dysfunction (generalized = delerium, seizures, coma OR focal = hallucinations, hemiparesis).

Anonymous  Noble p. 1557-1558  

Infection of the brain parenchyma and is most commonly viral, if bacterial it is called cerebritis. In North America, HSV, enterovirus (polio, echovirus, and coxsackievirus), and arbovirus are the most causative agents. Typical clinical features of encephalitis include fever, meningism, and signs of raised ICP. Reduction in consciousness level from drowsy to coma, seizures that are often focal, and various other focal signs also occur, depending on the areas of the brain affected by the inflammatory process. The combination of fever and meningism with evidence of cerebral dysfunction, either generalized (delirium, seizures, coma) or focal (hallucinations, hemiparesis) must make one consider encephalitis.

Anonymous Noble, p. 1558

Typical features of encephalitis include fever, meningism and signs of raised ICP. Reduction in consciousness level from drowsiness to coma, seizures that are often focal and various other focal signs also occur depending on which areas of the brain are affected by inflammatory process. Combination of fever and meningism with evidence of cerebral dysfunction, either generalized (delirium, seizures, coma) or focal 9hallucinations, hemiparesis and so forth) must make one consider encephalitis.

            12.    Identify acute viral encephalitis as an important cause of substantial mortality and serious neurological morbidity in survivors.

Aprilt Noble 2^nd ed. p. 1368.

OK.  It also talks about how these viruses get there by bitten by a misquito carrying a virus and occurs in summer and early fall.

Anonymous -HSV encephalitis has the highest morbidity and mortality of the common viral encephalitides.  Untreated, mortality = 70% with <5% survivors having normal neurological function.

-ICP monitoring is needed in severe cases.

Anonymous True

HSV encephalitis has the highest morbidity and mortality of the common viral encephalitides (untreated mortality 70%; <5% of survivors have normal neurological function). ICP monitoring is needed in severe cases. Prognosis is based on infecting agent, though still poor.

Anonymous

The incidence of the various types of viral encephalitis varies from year to year, depending on whether sporadic or epidemic outbreaks occur.  In relative terms, the incidence is about one-tenth that of bacterial meningitis.  The yearly incidence ranges form 20 to 2000 reported cases (US).  It has a 20% mortality rate in the elderly.  Disease is most severe in the very young, causing seizures in 90% of affected infants and permanent neurologic deficits in 50%.  There is a breakdown of the prognosis for each of the specific viruses responsible for encephalitis on page 1489 of Tintinalli

            13.    Identify herpes simplex encephalitis as presenting with focal neurological signs, requiring differences in diagnosis (e.g., MRI, CT, or possible brain  biopsy) and treatment  (e.g., IV acyclovir) .

Aprilt Noble 2^nd ed. 1369

OK.  It also talks about how HSV-1 has a focal focal encephalitis of the inferiorfrontal and temporal lobes with severe necrosis and intraneuronal inclusion bodies.  It enters the brain from a peripheral tract.  Cowdry type A inclusion bodies are seen.

Anonymous Current p. 1305, D.

Encephalitis and Recurrent Meningitis.

-Herpes simplex encephalitis presents with nonspecific symptoms:

flu-like prodrome

headache, fever, behavior and speech disturbances

seizures (focal or generalized)

-Distinguishing feature: tendency for temporal lobe to be involved (resulting in mass effect on imaging studies and temporal lobe seizure foci on EEGs)

-CSF WBC pleocytosis is common

-Rapid, sensitive and specific tool for Early Diagnosis: HSV DNA PCR in the CSF.

-Untreated disease + coma = high mortality rate. (Those who survive often have neurological sequelae).

Noble p. 1559.

-CSF features: increased pressure, increased protein, lymphocytes + RBCs present.

-Characteristic EEG pattern (including slow temporal region activity).

-CT scan: swelling/enlargement of temporal lobes that is asymmetrical.

-MRI: shows CT scan findings but even better.

-Diagnosis via: PCR of the CSF, fluorescent antibody staining or culture of brain biopsy.

-LP: may be dangerous b/c mass effect of lesion.  CT or MRI should be done 1^st to r/o presence of a pressure cone.

-Acyclovir reduces morbidity and mortality if given early.

Anonymous True  Noble p. 1559  

The CSF shows an increase in pressure and protein levels; lymphocytes and RBC’s are often present. A characteristic EEG pattern (diffuse, mainly temporal region slow activity with periodic discharges) is described but not specific. The CT scan may demonstrate swelling and enlargement of the temporal lobes (usually asymmetrically), although MRI shows this even better. The specific methods of diagnosis are PCR of the CSF, fluorescent antibody staining, or culture of brain biopsy specimen. Because of the mass effect of the lesion, LP may be dangerous and CT or MRI should be done first to R/O the presence of a pressure cone. Acyclovir reduces mortality and morbidity if it is given early, 10mg/kg q 8hx10 days, reduces mortality by 20%; half of the patients recover completely.

Anonymous

Clinical features: May have an acute or subacute onset. Typically, a few days of malaise, fever, HA, anorexia, nausea, and other nonspecific symptoms progress to a subtle changes of personality, with evolving depression, paranoia, or abnormal behavior and confusion. Photophobia, signs of raised ICP, meningeal irritation, and focal signs appear next; the latter include hemiparesis, facial weakness, dysphasia, dysarthria, decerebrate rigidity, ocular palsies or nystagmus, seizures, and in the late stages stupor or coma.

Although the whole brain is involved, the temporal lobes are particular affected. The CT scan may demonstrate swelling and enlargement of the temporal lobes (usually asymmetrically), although MRI scans show this even better. The specific method of Dx is PCR of the CSF, fluorescent antibody staining, or culture of the brain biopsy specimen. B/c of the mass effect of the lesion, LP may be dangerous and CT and MRI should be done first to R/O the presence of a pressure cone.

Treatment: Acyclovir reduces mortality and morbidity if it is given early, and the low toxicity of this drug has led to its use empirically in most cases of acute, sporadic encephalitis. Acyclovir, 10 mg/kg given IV q 8 h for 10 days, reduces mortality to about 20%; half of the pts completely recover.

Ravel chptr. 19

Compare CT and MRI and brain scanning.

Ravel 298-299

Most of this material is already covered in the objectives for meningitis. What is most important is learning the different CSF pictures for bacterial meningitis vs viral meningitis vs TB and fungal meningitis. Also worth reviewing is material comparing CT w/ MRI and brian scanning on pp. 298-9

Radionucleotide advantages:            No xray contrast media needed, lower cost, ability to inspect major blood vessels - flow studies.

CT advantages: CT over brain scan in ability to visualize ventricles, better detection of brain tumor, better specificity in brain lesions(more reliable in posterior fossa lesions), better delineation of CNS anatomy over MRI. Lower cost and better results in early CVA/hemorrhage (significantly better in subacute subdural or epidural hemorrhage) and ability to detect calcifications and bone detail.

MRI advantages: No radiation, sometimes better in lesions detection (than scan or CT) better tissue detail, better visualization of spinal cord, sometimes more specific diagnosis. (More cost, slower, problems with Pts. with cardiac pacers, internal metal objects and clostrophobia).

*Ct and MRI are about equal in diagnosing subdural hematoma (MRI more expensive though).

Different CSF (cerebral spinal fluid) pictures for bacterial vs viral vs TB  vs fungal meningitis.  

Ravel 294-295

General CSF info: CSF should be clear/colorless. It will be pink-red with blood present. It will be white with WBC/protein present and yellow if they are present over 4 hours.

                                    Glucose           Protein            Lactic Acid     Highest WBC counts

Bacterial                     low                   *elevated          elevated            polymorphonuclear

                                                                                    along with         neutrophils

                                                                                    leukocytosis      predominate

Viral                                                                            no elevated       lymphocytes or

                                                                                    or mild elev.      mononucleocytes

TB                               low                                           elevated            lymphocytes

                                                                                                            predominate

Fungal                         low                                           elevated            sometimes leuks.

                                                                                                            predominate, some-

                                                                                                            times neutrophilic

* Protein reaches adult levels after 6 months. It is higher in newborns-6mths. Generally protein in CSF increases proportionally to leukocytosis in CSF. Notify lab of Pt. age - scale is different!

In early infection glucose may  be normal. In metastasis and subarachnoid hemorrhage there may also be a low glucose.

CSF Cultures:           

1-2 Months:    1) Group B strep    2) E. Coli    3) Listeria monocytogenes/other bacteria

3mths-6yrs:     1) H. Flu    2) Meningococcus    3) pneumococcus

peds/adolesc: 1) meningococcus    2) pneumococcus

adults:             1) meningococcus    2) (some) pneumococcus    3) staphylococci

                                                                                                    (assoc. with surgery)

elderly:                        1) pneumococci    2) meningococci    3) gram neg./others

*A negative gram stain does not r/o acute bacterial meningitis

** Albuminocytologic dissociation = Marked protein elevation without corresponding CSF cell    increase. (Assoc w/ Guillain-Barre syndrome and Giant cell arteritis).

*** The most important change in CSF glucose is a decrease

****CSF pressure varies directly w/venous pressure and has no relationship to arterial pressure. Two most common causes of CSF pressure elevation: meningitis and subarachnoid hemorrhage.

III.       Cerebrospinal Fluid Examination

1.            Be able to describe the typical cerebrospinal fluid findings in the normal patient and in a patient with:

a.       Community acquired bacterial meningitis

b.      Mycobacterial or fungal meningitis

c.       Spirochetal meningitis

d.      Aseptic or viral meningitis and meningoencephalitis

e.       Neighborhood reaction (brain abcess, vertebral osteomyelitis, epidural abcess, subdural empyema, bacterial sinusitis or mastoiditis)

TIM CMDT pg 1253

Normal: 0-5 WBC’s/uL, glucose 45-85 mg/dL, protein 15-45 mg/dL, opening pressure= 70-180 mm H20

a.       Community acquired bacterial meningitis

Typically has between 200-2000 polymorphonuclear neutrophils; the glucose concentration is < 45 (low) mg/dL; the protein usually > 50 mg/dL.  The opening pressure is markedly elevated.

                CMDT pg 1253

b.      Mycobacterial or fungal meningitis

Typically has between 100-1000 WBC’s, mostly lymphocytes.  Glucose levels are < 45 mg/dL (low), protein > 50 (high) mg/dL. The opening pressure is moderately elevated.

                CMDT pg 1253

c.       Spirochetal meningitis

Typically has between 100-1000 WBC’s, mostly lymphocytes. Glucose levels are normal. Protein levels are > 50 (high) mg/dL. The opening pressure is normal to slightly elevated.

                CMDT pg 1253

d.      Aseptic or viral meningitis and meningoencephalitis

Typically between 25-2000 WBC’s, mostly lymphocytes. Glocose levels are normal or low.  Protein levels are > 50 (high) mg/dL. The opening pressure is slightly elevated.

e.       Neighborhood reaction (brain abscess, vertebral osteomyelitis, epidural abscess, subdural empyema, bacterial sinusitis or mastoiditis)

WBC’s are variably increased. Glucose levels are normal. Protein levels are normal or high.  The opening pressure is variable.

Anonymous Current p. 1253, Table 30-2

Typical CSF findings in various CNS diseases.

-Normal:

0-5 lymphos, 45-85 mg/dL glucose, 15-45 mg/dL protein, 70-80mm opening pressure.

-Purulent meningitis (bacterial) community acquired:

200-20,000 PMNs, low glucose (<45), high protein (>50), high opening pressure.

-Granulomatous meningitis (mycobacterial, fungal):

100-1,000 (mostly) lymphos, low glucose (<45), high protein (>50), semi high pressure.

-Spirochetal meningitis:

100-1,000 (mostly) lymphos, normal glucose, high protein (>50), maybe normal pressure.

-Aseptic meningitis, viral or meningoencephalitis:

25-2,000 (mostly) lymphos, normal or low glucose, high protein, slightly high pressure.

-Neighborhood reaction:

variably increased cells, normal glucose, normal or high protein, variable pressure.

Additional info:

-CSF glucose must be considered in relation to blood glucose level.  Normally, CSF glucose is 20-30 mg/dL lower than blood glucose (30-50% lower).

-In granulomatous, spirochetal and aseptic meningitis cases, PMNs may predominate (vs. lymphocytes found later) early on in the disease course.

-Neighborhood reaction may occur in mastoiditis, brain abscess, epidural abscess, sinusitis, septic thrombus, brain tumor.  CSF culture results usually negative.

IV.       Seizure Disorders

            1.      Distinguish between the following major categories of seizures.

                              partial seizures:

                                    simple partial seizures (focal)

                                    complex partial seizures (aka: psychomotor or temporal epilepsy)

                              generalized seizures:

                                    absence, or petit mal

                                    tonic-clonic, or grand mal

                                    status epilepticus

Kim R. CMDT pg 953

PARTIAL:

1. Simple partial (focal)- may be manifested by focal motor symptoms(convulsive jerking) or somatosensory symptoms(paresthesias or tingling) that spread to different parts of the limb or body depending upon their cortical representation.  In other instances, special sensory symptoms (light flashes or buzzing) indicate involvement of visual, auditory, olfactory, or gustatory regions of the brain, or there may be autonomic symptoms of signs(abnormal epigastric sensations, sweating, flushing, pupil dilation). 

2. Complex partial- impaired consciousness may be preceded, accompanied, or followed by the psychic symptoms mentioned above, and automatisms may occur.  Such seizures may also begin with some of the simple symptoms mentioned above.

GENERALIZED:

1. absence, or petit-mal- characterized by impairement of consciousness, sometimes with mild clonic, tonic, or atonic components(reduction or loss of postural tone), autonomic components(enuresis), or accompanying automatisms.  Onset and termination of attacks are abrupt.  If attack occur during conversation, the person may miss a few words or may break off in mid sentence for a few seconds.  The attack is so brief that the person may not be aware of it.  These type of seizures almost always begin in childhood and frequently cease by the age of 20, although occasionally they are replaced by other forms of generalized seizure.

2. Tonic-clonic, or grand mal- characterized by sudden loss of consciousness, the patient becomes rigid and falls to the ground, and respiration is arrested.  This tonic phase, which usually lasts for less than a minute, is followed by a clonic phase in which there is jerking of the body that may last for 2 to 3 minutes and is then followed by a stage of flaccid coma.  During the seizure the patient may bite his/her lip, tongue, loose bowel and bladder control.  Immediately after the seizure, the patient may either recover consciousness, drift into sleep, have further convulsion without recovery of consciousness between attacks (status epilepticus), or after recovering consciousness have a further convulsion (serial seizures).  In other cases, patients will behave in an abnormal fashion in the immediate postictal period, without subsequent awareness or memory of events (postepileptic automatism).  Headache, disorientation, confusion, drowsiness, nausea, soreness of muscles, or some combination of these symptoms commonly occurs postictally.

3. status epilepticus- convulsions without recovery of consciousness between attacks.

Anonymous Current p. 953.

-Partial seizures:

simple partial (focal) & Complex Partial (psychomotor/temporal epilepsy)

-Generalized seizures:

absence (petit mal) & tonic-clonic (grand mal) & status epilepticus

Simple Partial Seizures (Focal Seizures):

-Manifested by:            focal motor symptoms (convulsive jerks)

                                    somatosensory symptoms (paresthesias/tingling) that spread

                                    special sensory symptoms (light flashes, buzzing, etc.)

                                    autonomic symptoms (flush, sweat, pupils dilate, epigastric sxs)

                                    dysphagia

                                    dysmnesic symptoms (déjà vu)

                                    illusions

                                    affective disturbance

                                    hallucinations

(This is a list of potential manifestations; not all S/Sxs occur.)

-Complex Partial Seizures (Psychomotor or Temporal Epilepsy):

May be manifested by:  S/Sxs listed above.  Theses S/Sxs are generally accompanied, preceded or followed by impaired consciousness.  Automatisms may also occur.

-Absence Seizures (Petit Mal Seizures):

May be manifested by: impairment of consciousness

                                                mild clonic, tonic or atonic components (postural tone loss)

                                                autonomic components (enuresis)

                                                automatisms

                                                abrupt onset & termination of attacks

                                                breaking off in mid sentence for seconds if px is speaking

                                                very brief impairment of awareness

                                                patient is often unaware seizure occurred

                                                almost always begin in childhood

                                                seizures often stop by age 20

-Tonic-Clonic Seizures (Grand Mal Seizures):

May be manifested by:  sudden loss of consciousness

                                                patient becomes rigid and falls to ground

                                                respiration stops

                                                tongue or lip bites

                                                urinary or fecal incontinence

                                                patient injury

                                                tonic phase is 1^st and lasts < 1 minute

                                                clonic phase (jerking) is 2^nd and lasts up to 2-3 minutes  a stage of flaccid coma often follows the seizure

Immediately after the tonic-clonic seizure, the patient may recover consciousness, drift into sleep OR have a further convulsion without recovery of consciousness between attacks (STATUS EPILEPTICUS).  Headache, disorientation, confusion, drowsiness, nausea, soreness of muscles can all occur postictally.

Additional Info:

-Partial Seizures – only a restricted part of one cerebral hemisphere is activated with this seizure.  Partial seizures are subdivided into simple seizures, in which consciousnessis preserved, and complex seizures, in which it is impaired.

-Generalized Seizures – nothing special to say about these.  Generalized seizures include absence seizures, tonic-clonic seizures, status epilepticus, and others.

Anonymous  Noble 1485-1486

•        partial seizures (begin locally):

o simple partial seizures (focal) – without impairment of consciousness; diverse manifestation determined by the region of cortex activated by the seizure (may progress from thumb → hand → arm → shoulder → girdle → trunk → entire body.   They typically last 20-60 seconds

o complex partial seizures (aka: psychomotor or temporal epilepsy) – with impairment of consciousness lasting 30 sec to 2 minutes; often associated with purposeless movements such as lip smacking or hand wringing; confusion, amnesia, full coordination (i.e. dressing, undressing), and aura

o partial with secondarily generalized tonic-clonic seizure – when a simple or complex partial seizure evolves into a tonic-clonic seizure with loss of consciousness and sustained contractions (tonic) of muscles throughout the body, followed by periods of muscle contraction alternating with periods of relaxation (clonic), typically lasting 1-2 minutes; may be associated with ↑ heart rate, ↑ BP, and loss of bowel/bladder control.

•        generalized seizures (bilaterally symmetrical and without local onset):

o absence (aka petit mal) – abrupt onset of impaired consciousness with staring and cessation of ongoing activities typically lasting less than 30 seconds; common in children, usually disappears after adolescence.

o tonic-clonic (aka grand mal) – NOT preceded by a partial seizure; loss of consciousness and sustained contractions (tonic) of muscles throughout the body, followed by periods of muscle contraction alternating with periods of relaxation (clonic), typically lasting 1-2 minutes; may be associated with ↑ heart rate, ↑ BP, and loss of bowel/bladder control.  A vocal “cry” or “scream” sometimes occurs as the result of air being expelled through the contracted vocal cords.

o status epilepticus (prolonged partial or generalized seizures without recovery from attacks) – life-threatening emergency requiring immediate medical management along with anti-epileptic drugs; seizure episodes last > 30 minutes or intermittently > 30 minutes without a regain in consciousness

o febrile seizure – seizure in healthy infants and children (6mo – 5yr) associated with a fever > 38.0 C (rectal) without evidence of intracranial infection or defined cause

Anonymous

Partial seizures:  begin in one area of the brain and initially produce symptoms that are referable to the region of cortex involved.

Simple partial seizures (focal): focal neurologic events in which consciousness remains intact.

Complex partial seizures (aka: psychomotor or temporal epilepsy):  consciousness is impaired.

Generalized seizures: bilaterally symmetric and without focal onset.  An episode may begin with a premonitory aura that is followed by a sudden loss of consciousness.  A tonic phase of limb extension ensues, lasting 10 to 30 seconds, followed by a clonic phase of limb jerking of at least 30 seconds.  The patient then becomes flaccid and comatose before regaining consciousness.  Postictal confusion is characteristic and can last for hours, although 10 to 30 minutes is more typical.  Tongue biting and incontinence are other characteristic features.

Absence, or petit mal:  very brief, generally lasting only a few seconds.  The patient suddenly loses consciousness without losing postural tone. They appear confused, detached, or withdrawn, and current activity ceases.  They may stare and have twitching of their eyelids.  They do not respond to voice or to other stimulation, exhibit voluntary movements, or lose continence.  The attack ceases abruptly, and the patients are able to resume their previous activity with no postictal symptoms.  Both the patients and witnesses may be unaware that anything has happened.  Classic absence seizures are limited to school-aged children and are often attributed by parents and teachers to daydreaming or not paying attention.  The attacks may be very frequent, sometimes occurring 100 or more times daily, and may result in poor school performance.  They usually resolve as the child matures.  (Tintinalli 1463)

Tonic-clonic, or grand mal:  they begin with abrupt loss of consciousness; there is usually no warning or aura.  In a typical attack, the patient suddenly becomes rigid, trunk and extremities are extended, and the patient falls to the ground.  Patients are often apneic during this period and may be deeply cyanotic.  

Status epilepticus: defined as either continuous seizure activity for 30 minutes or more, or two or more seizures that occur without full recovery of consciousness between the attacks.

            2.      Identify the main elements of the history, physical examination, and diagnostic tests which are obtained in working up a patient with seizure disorder.

Kim R. CMDT pg 954

HX: nonspecific changes such as HA, mood alterations, lethargy, and myoclonic jerking.  A sense of an aura may precede an attack.

PE: the presence of lateralized or focal signs postically suggests that seizures may have a focal origin.  In pts with symptomatic epilepsy, the findings on exam will reflect the underlying cause.

TESTS: MRI is indicated for pts with focal neurologic symptoms of signs, focal seizures, or EEG findings of focal disturbances; some clinicians order imaging studies for all patients with new-onset seizure disorder.  EEG supports the clinical DX of epilepsy. LABS: CBC, blood glucose, liver and renal function tests, and serologic testing for syphilis. 

Anonymous Current p. 954.

-History:  Headache, mood alterations, lethargy, myoclonic jerking can occur hours before seizures.  Auras can occur minutes or seconds before seizures.  Sometimes seizures occur at specific times (like during sleep).  Sometimes seizures occur in relation to external precipitants (like lack of sleep, missed meals, stress, menstruation, alcohol consumption or withdrawal, drug use).  Fever and infections can precipitate seizures in known epileptics, as can flashing lights, flickering tvs, music and reading.

-Physical Exam:  Clinical exam between seizures shows no abnormality in patients with idiopathic epilepsy, but in the immediate postictal period, exstensor plantar responses may be seen.  The presence of lateralized or focal signs postictally suggests that seizures may have a focal origin.  In patients with symptomatic epilepsy, the findings on exam will reflect the underlying cause.

-Diagnostic Tests:

~MRI for patients with ANY focal S/Sx.  Order imaging studies for all patients with new onset seizure disorders, especially if the disorder is progressive or if patients are over 20 years of age.  Also get a CXR in such patients (lungs are common site for primary and secondary neoplasms).

~Full blood count

~Blood glucose

~Liver and renal function tests

~Serologic tests for syphilis

~EEG

Anonymous  Noble 1488, Goroll 964-965

• History – essential to gain exact description of events from both patient and a witness

o       Questions:  What happened just before you lost consciousness?  Do you ever have a warning or a feeling that you are going to have a seizure?  Do you ever think you are going to have a seizure and it doesn’t occur?  Were you injured during the convulsion?  Did you lose control of your bladder or bowels?

o       History of head injury and an estimate of its severity, previous  intracranial sepsis (meningitis or encephalitis), birth and developmental milestones, and a family history of seizures or other neurological disorders

o       Other areas include drugs (etoh, cocaine, meth, antidepressants, sedatives, theophyllin, insulin, diuretics), cardiac arrhythmias, valvular disease, previous malignancy, and stroke

o       History of febrile seizures in childhood should be distinguished from the pt’s habitual seizure disorder

o       Pt’s state after the ictus – how long before they return to awareness, is there any limb paralysis or dysphasia?

• PE:

o       Evaluate for signs of hypo/hyperglycemia, meningeal irritation (stiff neck, HA)

o       Neurological exam

o       Check for postural hypotension, abnormalities in heart rate and rhythm, head trauma, carotid disease, cardiac disease, systemic infection, and signs of alcohol or drug abuse

• Diagnostic tests:

o       Electroencephalography (EEG) – abnormal EEG with epileptiform features such as spikes or sharp waves supports the dx of seizures and may provide information about the type of seizure disorder; there are limitations in that an abnormal pattern is not adequate for diagnosis, and a normal EEG can be found in up to 20% of patients with seizures

o       Neuroimaging:

•   MRI (with/without contrast) – more sensitive than CT, may be more useful in demonstrating abnormalities in the medial temporal region

•   CT scan – may be sufficient in pts who have had a history of brain insult that could explain the etiology of the seizure disorder

•   Positron emission tomography (PET) and single-photon emission computed tomography (SPECT) – may confirm the presence of an organic abnormality and provide an outline of the abnormal region for which surgical treatment might be considered

o       Other testing:

•   Blood chemistries, electrolytes, calcium, etoh, and toxic screens are important

•   All pts with risk factors for HIV should be tested

•   Lumbar puncture if evidence of infection is found (this is not routine for first seizure)

Anonymous   Tintinalli p. 1464-66

History:  Important avenues of inquiry include preceding aura, abrupt or gradual onset, progression of motor activity, loss of bowel or bladder control, and whether the activity was local or generalized, symmetrical or not.  The duration of the attack and any postictal confusion or lethargy should be sought.  The patient should be asked whether he or she has any recollection of the attack.  If the patient is a known epileptic, the baseline seizure pattern should be established.  If there is no previous history of seizures, a more detailed history is needed. Symptoms that might suggest previous unwitnessed or unrecognized seizures, such as blank or staring spells in school, involuntary movements, unexplained injuries, nocturnal tongue biting, and enuresis, may be clues to a more long-standing problem.  A history of recent or remote head injury should be sought.  Concurrent pregnancy or recent delivery suggests the possibility of eclampsia.  A history of metabolic derangements or electrolyte abnormalities, hypoxia, systemic illness (esp. CA), coagulopathy or anticoagulation, drug ingestion or withdrawal and alcohol use may help identify factors that predispose patients to seizures.

PE:  The PE should be directed toward discovering any injuries, especially head or spine that might have resulted from the seizure.  Fractures, sprains, bruises and posterior dislocations of the shoulder are common and may be overlooked.  Tongue lacerations and aspiration are frequent sequelae.  A search for any systemic illness that may have caused the attack should be undertaken.  Temperature should be noted.

Diagnostic Tests:  With the patient who has a history of seizure disorder, the only test that may be needed is an anticonvulsant level.  In the case of a patient with a first seizure or when the history is unclear:

Glucose

Electrolytes

BUN

Creatinine

Calcium

Magnesium

Pregnancy test

Toxicology screen

UA (if hemoglobin positive, but no red cells, then a CPK should be done to rule out rhabdomyolysis.)

            3.      Identify each of the following as a common cause of acute or recurrent seizure disorder.

                              idiopathic epilepsy

                              metabolic and toxic encephalopathies

                              posttraumatic epilepsy (especially penetrating head injuries)

                              CNS neoplasms

                              cerebrovascular disease

                              intracranial infection

Kim R. CMDT pg 953

1.   Idiopathic epilepsy- seizures usually begin between 5 and 20 years of age, but may start later in life.  No specific cause is known and there is no other neurologic abnormality.

2. Metabolic and toxic enephalopathies-withdrawl from alcohol or drugs is a common cause of recurrent seizures, and other metabolic disorders such as uremia and hypoglycemia or hyperglycemia may also be responsible.

3. posttraumatic epilepsy- trauma is an important cause of seizures at any age, but especially in young adults.  Posttraumatic epilepsy is more likely to develop if the dura mater was penetrated and generally becomes manifest within 2 years following injury. 

4. CNS neoplasms-these may lead to seizures at any age, but they are an especially important cause of seizures in middle and later life, when the incidence of neoplastic disease increases.  The seizures are commonly the initial symptoms of the tumor and often are partial(focal) in character.  They are most likely to occur with structural lesions involving the frontal, parietal, or temporal regions.  Tumors must be excluded by appropriate imaging studies in all pts with onset of seizures after 30 years of age, focal seizures or signs, or a progressive seizure disorder.

5. cerebrovascular disease- is becoming an increasingly frequent cause of seizures with advancing age and are the most common cause of seizures with onset at age 60 years or older.

6. intracranial infection- infectious disease must be considered in all age groups as potentially reversible causes of seizures.  Seizures may occur with an acute infective or inflammatory illness, such as bacterial meningitis or herpes encephalitis, or in pts with more long-standing or chronic disorders such as neurosyphilis or cerebral cysticerosis.  In pts with AIDS, they may result from CNS toxoplasmosis, crytococcal meningitis, secondary viral encephalitis, or other infective complications.  Seizures are a common sequela of supratentorial brain abscess, developing most frequently in the first year after treatment.

Anonymous Current p. 953.

-Idiopathic Epilepsy:

aka Constitutional Epilepsy

seizures usually begin between 5 and 20 years of age 

no identifiable cause

no neurologic abnormality

-Metabolic and Toxic Encephalopathies:

a type of symptomatic epilepsy (vs. idiopathic epilepsy)

commonly caused by drug or alcohol withdrawal

commonly caused by metabolic disorders like uremia, hypoglycemia, hyperglycemia      

-Posttraumatic Epilepsy (especially penetrating head injuries):

especially seen in young adults

this epilepsy is more likely to develop if the dura mater is penetrated

manifestation can occur up to 2 years post injury

seizures occurring immediately after injury do not imply that future attacks are a given

-CNS Neoplasms:

neoplasms can lead to seizure at any age

neoplasms are more likely in middle and later life

if middle/later life pxs present w/ seizures r/o neoplasm-common things occur commonly

these seizures are often initial symptom of the tumor

these seizures are often partial (focal)

*Tumors must be excluded by appropriate imaging studies in all patients with onset of seizures after 30 years of age, focal seizures or signs, or a progressive seizure disorder.

-Cerebrovascular Disease:

vascular diseases become increasingly frequent cause of seizures with advancing age

for seizure onset at age 60 or above, vascular disease is most likely cause

-Intracranial Infection:

infection must be considered in all age groups presenting with seizures

infections are a potentially reversible cause of seizures (so they’re a Do Not Miss)

possible acute causes – bacterial meningitis, HSV encephalitis

possible chronic causes – neurosyphilis, cerebral cysticerosis

possible AIDS related causes – toxo, crypto

-Degenerative Disorders (I added this one to the list b/c it’s in the book):

Alzheimer’s disease and other degenerative disorders are a cause of seizures in later life.

Anonymous  Goroll 963-4

• Primary or idiopathic epilepsy – most common cause of recurrent seizures in children

o       In the young adult (18-45) population, the demonstrated causes include drugs, neoplasm, and trauma

o       In the older adult population , underlying pathology is equally divided among neoplasm, trauma, and CV disease

• Metabolic and toxic encephalopathies – A nonepileptic convulsion may occur in the context of a transient metabolic disturbance, such as cerebral hypoperfusion, hypoglycemia, a hyperosmolar state, or hyponatremia

• Posttraumatic epilepsy – higher incidence with penetrating head injuries and severe trauma causing a loss of consciousness for more than a half hour; also if there was a lobar hematoma or depressed skull fracture

o       With a history of closed head injury, epilepsy usually develops within 2 years, whereas with open head trauma, seizures may develop at a longer interval after the original injury

• CNS neoplasms

• cerebrovascular disease

• intracranial infection

Anonymous

Idiopathic epilepsy -  most common cause of recurrent seizures in children, but increasingly rare in the young adult population.

Metabolic and toxic encephalopathies - common cause of seizures in young adult and older adult populations. Metabolic more common in older adults. Toxic includes alcohol (common cause in young adults), prescription drugs, street drugs, and ingestion of toxic substances.

Posttraumatic epilepsy (especially penetrating head injuries) - common cause of seizures in the young adult population.

CNS neoplasm’s -  common cause of seizures in young adult population and accounts for ~1/3 of seizures in older adult population.

Cerebrovascular disease - Common cause of seizures in older adult population (~1/3 of cases).

Intracranial infection -  Less common cause of seizures, more common in pediatric population.

Goroll, p. 964, Noble, p. 1485

            4.      Read the material about treatment of seizure disorders, but  pharmacology questions will be deferred to the Patient Management  course.

Anonymous Current p. 955.

V.        Multiple Sclerosis

            1.      Identify multiple sclerosis (MS) as the most common chronic neurologic disease of young adults.

Stephen CMDT pg 983

This common neurologic disorder, which probably has an autoimmune basis, has its greatest incidence in young adults.

Anonymous Current p. 983.

This common neurologic disorder, which probably has an autoimmune basis, has its greatest incidence in young adults.

Anonymous  Noble p. 1623

MS rarely occurs in children or the elderly; most pts develop their first Sx between the ages of 20 and 40 (30 is average age of onset). There is increasing prevalence at latitudes farthest from the equator – therefore more common in Washington. About 20% of pts have a FH of this disorder, which is strong evidence for genetic influences in MS.

Anonymous  Noble p. 1623

MS rarely occurs in children or the elderly; most pts develop their first Sx between the ages of 20 and 40 (30 is ave. age of onset). There is increasing prevalence at latitudes farthest from the equator – therefore more common in Washington. About 20% of pts have a FH of this disorder, which is strong evidence for genetic influences in MS.

            2.      Recognize that the most popular current theory of MS is that it is an autoimmune, inflammatory demyelinating disorder of the CNS resulting in the delay, dispersion, and blockage of electrical impulses.

Stephen

OK!!

Anonymous Current p. 983.

Pathologically, focal areas of demyelination with reactive gliosis are found scattered in the white matter of brain and spinal cord and in the optic nerves.

Noble p. 1623.

MS is a recurrent progressive disorder whose signs and symptoms are due to plaques of demyelination in the white matter of the brain.  Changes in the blood-brain barrier initiate new lesions and axonal damage is likely responsible for progression.  It is an autoimmune, inflammatory, demyelinating disorder resulting in the delay, dispersion and blockage of electrical impulses.

Anonymous  Noble 1623

Recurrent, progressive disorder whose signs and symptoms are due to plaques of demyelination in the white matter of the brain.  Changes in the blood-brain barrier initiate new lesions, and axonal damage is likely responsible for progression.  It is an autoimmune, inflammatory, demyelinating disorder resulting in the delay, dispersion and blockage of electrical impulses.

Anonymous Noble 1623

Recurrent, progressive disorder whose signs and symptoms are due to plaques of demyelination in the white matter of the brain.  Changes in the blood-brain barrier initiate new lesions, and axonal damage is likely responsible for progression.  It is an autoimmune, inflammatory, demyelinating disorder resulting in the delay, dispersion and blockage of electrical impulses.

            3.      Describe various clinical manifestations of MS, especially the following:

                              visual disturbances: optic neuritis, nystagmus, diplopia,

                              paresthesias/dysesthesias,

                              spasticity, limb weakness, and ataxia,

                              urinary urgency, frequency, or incontinence,

                              disorders of mental function.

Stephen CMDT pg 985

Visual disturbances

Optic atrophy, nystagmus, and diplopia

Parathesias/dysesthesias

Altered sensations, weakness, nunbness, and tingling.

Spasticity Conn’s Current Therapy pg 901

Spasticity results from interruption of inhibitory influiences on anterior horn cells that can occur with lesions of the brain, spinal cord, and brain stem. It is associated with increased muscle tone, weakness, hyperreflexia, extensor plantar responses, and spontaneous muscle spasms.

Disturbances of balance, gait or coordination.

Urinary urgency , frequency, or incontinence CMDT pg 983 result from sphincter disturbance.

Conn’s pg 902 Urinary freq., urgency, and subsequent urge incontinence usually result from a spastic detrusor muscle. Urinary retention and hesitation result from sphincter dyssynergia, with incomplete relaxation of internal and external sphincters during detrusor contraction.

Disorders of mental function Conn’s pg 901

Affective disorders and anxiety disorders are common in MS, and pts with MS are at increased risk for suicide.

Pts with MS can also experience inappropriate laughter or crying as a result of bilateral disruption of subcortical pathways.

Anonymous Goroll 975.

-Visual Disturbances: Optic Neuritis, Nystagmus, Diplopia

~Optic neuritis is characterized by unilateral vision loss that develops suddenly.  Optic neuritis is particularly associated with demyelinating disease, occurring in patients known to have MS and as a 1^st manifestation of the disease in others.  In patients with clinically isolated optic neuritis, as many as 75% will have developed clinically definite MS within 15 years.  (Current p. 166)

~Nystagmus in the abducting eye and a failure of adduction are often noted in MS patients.

~Diplopia resulting from internuclear ophthalmoplegia or an oculomotor deficit is another common symptom heralding MS.  Bilateral internuclear ophthalmoplegia is very characteristic of MS and strongly suggests the diagnosis.

-Paresthesias/Dyesthesias – see below (paraparesis is only thing I found).

-Spasticity, Limb Weakness & Ataxia – The common initial presentation of MS is usually weakness, numbness, tingling or unsteadiness in a limb; spastic paraparesis; retrobulbar neuritis; diplopia; disequilibrium; or a sphincter disturbance such as urinary urgency or hesitancy.  Symptoms may disappear after a few days or weeks but examination often reveals a residual deficit.  (Current p. 983)

-More on Ataxia – Ataxia and intention tremor are manifestations of cerebellar involvement.  Re: motor deficits, legs are more likely to be involved than arms, initially asymmetrically.

-Urinary Urgency, Frequency or Incontinence – see above (sphincter disturbance…).  Urinary problems are consequences of upper motor nerve injury in the spinal cord.

-Disorders of Mental Function – Later in the course of illness, cerebral involvement may produce memory loss, personality change and emotional lability.  More than 60% of MS patients demonstrate abnormalities on formal neuropsychiatric testing, even if asymptomatic.

Anonymous  Goroll, pp. 975-976

Clinical Presentation is a function of the site of the inflammatory process. Attacks are by definition those that produce symptoms that last more than 24 hours. They average up to one per year and decrease in frequency over time. Transient sensory deficits are the most common initial presentation, affecting about 40% to 50% of patients.

Paresthesias or diminution of sensation in the upper or lower extremities. The sensory disturbance may be bilateral and symmetric, extending to involve the adjacent trunk. About 15% to 20% experience acute monocular visual loss because of optic neuritis. A central scotoma, transient pain on eye movement, and decreased pupillary reaction to light (Marcus-Gunn pupil) are characteristic features.

Diplopia resulting from internuclear ophthalmoplegia or an oculomotor defect is another common symptom heralding MS. Bilateral internuclear ophthalmoplegia is very characteristic of MS and strongly suggests the diagnosis. A failure of adduction and coarse nystagmus in the abducting eye are noted. Other oculomotor functions remain intact.

Ataxia and intention tremor are manifestations of cerebellar involvement. Motor deficits may occur acutely or insidiously, with the insidious variety particularly common in older patients. Legs are more likely to be involved than arms, initially asymmetrically. However, upturned toes are common bilaterally, even in patients with unilateral problems.

Urinary difficulties (frequency, urgency, incontinence) are consequences of upper motor nerve injury in the spinal cord. The external sphincter fails to relax adequately, causing incomplete emptying. Such autonomic injury may also produce constipation and impotence.

Later in the course of illness, cerebral involvement may produce memory loss, personality change, and emotional lability. More than 60% of MS patients demonstrate abnormalities on formal neuropsychiatric testing, even if asymptomatic. Paroxysmal symptoms may result from dysfunction of partially demyelinated axons and simulate a transient ischemic attack or focal seizure, or produce an attack of tic douloureux.  Fatigue may be prominent and even predate exacerbations

Anonymous

Visual disturbances: optic neuritis, nystagmus, diplopia, paresthesias/ dysesthesias, spasticity, limb weakness, and ataxia, urinary urgency, frequency, or incontinence, disorders of mental function.  Goroll, pp. 975-976.

Clinical Presentation is a function of the site of the inflammatory process. Attacks are by definition those that produce symptoms that last more than 24 hours. They average up to one per year and decrease in frequency over time. Transient sensory deficits are the most common initial presentation, affecting about 40% to 50% of patients.

Paresthesias or diminution of sensation in the upper or lower extremities. The sensory disturbance may be bilateral and symmetric, extending to involve the adjacent trunk. About 15% to 20% experience acute monocular visual loss because of optic neuritis. A central scotoma, transient pain on eye movement, and decreased pupillary reaction to light (Marcus-Gunn pupil) are characteristic features.

Diplopia resulting from internuclear ophthalmoplegia or an oculomotor defect is another common symptom heralding MS. Bilateral internuclear ophthalmoplegia is very characteristic of MS and strongly suggests the diagnosis. A failure of adduction and coarse nystagmus in the abducting eye are noted. Other oculomotor functions remain intact.

Ataxia and intention tremor are manifestations of cerebellar involvement. Motor deficits may occur acutely or insidiously, with the insidious variety particularly common in older patients. Legs are more likely to be involved than arms, initially asymmetrically. However, upturned toes are common bilaterally, even in patients with unilateral problems.

Urinary difficulties (frequency, urgency, incontinence) are consequences of upper motor nerve injury in the spinal cord. The external sphincter fails to relax adequately, causing incomplete emptying. Such autonomic injury may also produce constipation and impotence.

Later in the course of illness, cerebral involvement may produce memory loss, personality change, and emotional lability. More than 60% of MS patients demonstrate abnormalities on formal neuropsychiatric testing, even if asymptomatic. Paroxysmal symptoms may result from dysfunction of partially demyelinated axons and simulate a transient ischemic attack or focal seizure, or produce an attack of tic douloureux.  Fatigue may be prominent and even predate exacerbations

            4.      Recognize that the natural history of MS is very variable; identify factors which may precipitate symptoms or attacks.

Stephen CMDT pg 983

A number of factors (eg, infection, trauma) may precipitate or trigger exacerbations.

Relapses are also more likely during the 2 or 3 months following pregnancy, possibly because of the increased demands and stressors that occur in the postpartum period.

Anonymous Current p. 983.

A number of factors may precipitate or trigger exacerbations (infection, trauma, etc.).  Relapses are also more likely during the 2 or 3 months following pregnancy, possibly b/c of the increased demands and stresses that occur in the postpartum period.

Noble Chapter 171.

Factors that may precipitate symptoms or attacks:

Acute infections, postpartum, hot baths, exercise, hot humid weather, physical and emotional stress.

Anonymous    Noble Ch. 171

Factors that may precipitate symptoms or attacks are:

• -Acute infections

• -6 mo. postpartum w/o pregnancy

• -Hot baths

• -Exercise

• -Hot humid weather

• -Physical/emotional stress

Anonymous Noble Ch. 171

Factors that may precipitate symptoms or attacks are:

-Acute infections

-6 mo. postpartum w/o pregnancy

-Hot baths

-Exercise

-Hot humid weather

-Physical/emotional stress

            5.      Identify diagnostic tests which help confirm the diagnosis of MS.

Stephen CMDT

MS should not be diagnosed unless there is evidence that two or more different regions of the central white matter have been affected at different times. The diagmosis is probable in pts with multifocal white matter disease, but only on clinical attack, or with a histoty of at least two clinical attacks but signs of only a single lesion.

MRI of the brain or cervical cord is often helpful in demonstrating the presence of a multiplicity of lesions. CT scans are less helpful.

Anonymous Conn’s 897 MRI is the most sensitive measure of disease activity in MS.

Goroll p. 976, Noble p. 1625.

-MRI is the most sensitive diagnostic testing tool for MS.  More than 90% of MS patients have multiple periventricular plaques (white matter lesions).

-CSF reveals abnormalities in 95% of MS patients.

Anonymous  Goroll 976

•      Along with the development of signs and symptoms of MS there are some diagnostic tests that can aid

         in diagnosing this disease.

•      Lab studies may help support the diagnosis, but no single lab test is diagnostic and clinical evidence is

               necessary for a diagnosis.

•      MRI is the most sensitive test.  More than 90%  of MS patients have multiple periventricular plaques

   (white matter lesions), presenting as areas of increased signal intensity on long TR-weighted

   and proton density-weighted images.  The problem is that these plaques also appear in normal

   aging, chronic uncontrolled HTN, advanced lyme disease and CNS vasculitis.

•      The CSF reveals abnormalities in 95% of MS patients including the following:

•      Moderate increase in cell count and protein are common but not specific.

•      Increase in IgG and oligoclonal IgG bands on electrophoresis are more specific

•      (Noble pg 1625 says only 30% of MS patients have increase cell counts and mostly lymphocytes)

•      Evidence of MS may also be supported by visual or auditory evoked potentials being abnormal in

demyelinated tracts. (impulses are slower in remyelinated areas)

            6.      Describe the role of corticosteroids and beta-interferon in the treatment of MS.

Jennyb Current p 984

Recovery from acute relapses may be hastened by treatment with corticosteroids, but the extent of recovery is unchanged.  Long-term treatment with steroids provides on benefit and does not prevent further relapses.

In pts with relapsing-remitting or secondary progressive disease treatment with beta interferon reduces the frequency of exacerbations.

Anonymous Current p. 984.

-Corticosteroids can speed recovery from acute relapses but extent of recovery is not changed.  Longterm treatment with steroids provides no benefit and does not prevent further relapses.

-Beta interferon treatment reduces frequency of exacerbations in patients with relapsing-remitting or secondary progressive disease. (Interferons can alter the course of the disease.)

Anonymous  Noble 1626, Goroll 976

•      Corticosteroids have proven to be beneficial in treating acute attacks of MS by marginally improving the signs and symptoms.  High dose methylprednisolone (pulsed therapy) is often used to treat the acute attacks.

•      Interferons have been shown to be beneficial in MS and were the first agents shown to alter the course of the disease.  Interferon Beta-1a reduces the number and severity of attacks and also may modestly alter the progression of the disease.

•      Interferon beta-1a include Avonex and Rebif

•      Interferon beta-1b include Betaseron

•      Studies show that it is important to start the disease modifying agents early in the course of MS as MRI

      studies have shown that the inflammatory process is active in many patients during

      clinical remission and irreversible axonal injury accumulates with time even durin