Meningitis
Introduction
Meningitis is inflammation of the meninges
that results in the occurrence of meningeal symptoms (eg, headache, nuchal rigidity, photophobia) and an increased number of white blood cells in the cerebrospinal fluid (CSF), ie, pleocytosis.
Depending on the duration of symptoms,
meningitis may be classified as acute or chronic. Acute meningitis denotes the evolution of symptoms within hours to several days. Chronic meningitis has an onset and duration of weeks to months. The duration of symptoms of chronic meningitis characteristically is at least 4 weeks.
Etiology
Acute bacterial meningitis denotes a
bacterial cause of this syndrome. This is usually characterized by an acute onset of meningeal symptoms and neutrophilic pleocytosis. Depending on the specific bacterial cause, the syndrome may be called, for example, Streptococcus pneumoniae meningitis, meningococcal meningitis, or Haemophilus influenzae meningitis.
Fungal and parasitic causes of meningitis
are also termed according to their specific etiologic agent, such as cryptococcal meningitis, Histoplasma meningitis, and amebic meningoencephalitis. Aseptic meningitis is a broad term that denotes a nonpyogenic cellular response, which may be caused by many different etiologic agents
Pathophysiology
Portals of entry into CNS : Invasion of the bloodstream (ie, bacteremia,
viremia, fungemia, parasitemia) and subsequent hematogenous seeding of the CNS, which is the most common mode of spread for most agents (eg, meningococcal, cryptococcal, syphilitic, and pneumococcal meningitis). Retrograde neuronal (ie, olfactory and peripheral nerves) pathway (eg, Naegleria fowleri, Gnathostoma spinigerum). Direct contiguous spread (ie, sinusitis, otitis media, congenital malformations, trauma, direct inoculation during intracranial manipulation).
Vascular endothelial injury and increased
BBB permeability lead to the entry of many blood components into the subarachnoid space. This contributes to vasogenic edema and elevated CSF protein.
The ensuing cerebral edema (ie, vasogenic,
cytotoxic, interstitial) significantly contributes to intracranial hypertension and a consequent decrease in cerebral blood flow. Anaerobic metabolism ensues, which contributes to increased lactate concentration and hypoglycorrhachia
Morbidity and Mortality
The mortality rate for viral meningitis
(without encephalitis) is less than 1%. Overall mortality rate from bacterial meningitis remains alarmingly high. It is reported to be approximately 25%. Among the common causes of acute bacterial meningitis, the highest mortality rate is observed with pneumococcus
•. Common Bacterial Pathogens Based on Age and Predisposing Risks
•Risk and/or Predisposing •Bacterial Pathogen Factor •Age 0-4 weeks •S agalactiae (group B streptococci) E coli K1 L monocytogenes •Age 4-12 weeks •S agalactiae E coli H influenzae S pneumoniae N meningitidis
•Age 3 months to 18 years •N meningitidis S pneumoniae H influenzae •Age 18-50 years •S pneumoniae N meningitidis H influenzae •Age older than 50 years •S pneumoniae N meningitidis L monocytogenes Aerobic gram-negative bacilli
•Immunocompromised state
•Intracranial manipulation, including neurosurgery
•Basilar skull fracture
•S pneumoniae N meningitidis L monocytogenes Aerobic gram-negative bacilli •Staphylococcus aureus Coagulase-negative staphylococci Aerobic gram-negative bacilli, including Pseudomonas aeruginosa •S pneumoniae H influenzae Group A streptococci
•CSF shunts
•Coagulase-negative staphylococci S aureus Aerobic gram-negative bacilli Propionibacterium acnes
Clinical features
The classic presentation of meningitis
includes fever, headache, neck stiffness, photophobia, nausea, vomiting, and signs of cerebral dysfunction (eg, lethargy, confusion, coma). The triad of fever, nuchal rigidity, and change in mental status is found in only two thirds of patients.
Signs of cerebral dysfunction are common,
including confusion, irritability, delirium, and coma. These are usually accompanied by fever and photophobia. Signs of meningeal irritation are observed only in approximately 50% of patients with bacterial meningitis, and their absence certainly does not rule out meningitis
Cranial nerve palsies may be observed as a result
of increased ICP or the presence of exudates encasing the nerve roots. Focal neurologic signs may develop as a result of ischemia from vascular inflammation and thrombosis. Seizures occur in approximately 30% of patients. Papilledema and other signs of increased ICP may be present
Differentials
Noninfectious meningitis, including
medication-induced meningeal inflammation Meningeal carcinomatosis CNS vasculitis Stroke Encephalitis
Investigations
CSF study is the mainstay of diagnosis
CSF Picture of Meningitis According to Etiologic Agent
•Age •Ope •WBC nt ning count Pres per mL sure •Bact •200 •100erial -300 5000; meni >80% ngitis PMNs * •Glu cose (mg/ dL) •<40 •Pro •Microbiology tein (mg /dL) •>10 •Specific pathogen 0 demonstrated in 60% of Gram stains and 80% of cultures
O.P TLC
Sugar
Protein •Viral isolation, PCR† assays
•Viral •9 •10•Normal, •Normal menin 0 300; reduced in but may be gitis - lymph LCM and slightly 2 ocytes mumps elevated 0 0 •Tuber •1 •100- •Reduced, •Elevated, culous 8 500; <40 >100 menin 0 lymph gitis - ocytes 3 0 0
•Acid-fast bacillus stain, culture, PCR
Management
Antibiotics
Empiric Antibiotics According to Predisposing Factors
Predisposing Feature Antibiotic(s) Age 0-4 weeks Ampicillin plus cefotaxime or an aminoglycoside Age 1-3 months Ampicillin plus cefotaxime plus vancomycin* Age 3 months to 50 Ceftriaxone or cefotaxime plus years vancomycin* Age older than 50 Ampicillin plus ceftriaxone or years cefotaxime plus vancomycin* Impaired cellular Ampicillin plus ceftazidime plus immunity vancomycin* Neurosurgery, head Vancomycin plus ceftazidime trauma, or CSF shunt
Brain Abscess
Introduction
Intracranial abscesses are uncommon,
serious, life-threatening infections. They include brain abscess and subdural or extradural empyema and are classified according to the anatomical location or the etiologic agent
Intracranial abscesses can originate from – infection of contiguous structures (eg, otitis media, dental infection, mastoiditis, sinusitis) – secondary to hematogenous spread from a remote site (especially in patients with cyanotic congenital heart disease), – after skull trauma or surgery – following meningitis. – In at least 15% of cases, no source can be identified.
Pathophysiology
Brain abscess is caused by intracranial
inflammation with subsequent abscess formation. Contiguous suppurative focus (45-50% of cases Trauma (10% of cases) Hematogenous spread from a distant focus (25% of cases)
Clinical features
In about two thirds of patients, symptoms
are present for 2 weeks or less. The clinical course ranges from indolent to fulminant. Most symptoms are a result of the size and location of the space-occupying lesion(s). The triad of fever, headache, and focal neurologic deficit occurs in less than half of patients.
The frequency of common symptoms and signs is
as follows:
– – – – – – – – Headache- 70%; mental status changes -65%; focal neurologic deficits- 65%; Fever- 50%; Seizures - 25-35%; nausea and vomiting - 40%; nuchal rigidity- 25%; Papilledema - 25%.
Low- or high-grade fever Persistent headache (often localized) Drowsiness ,Confusion, Stupor General or focal seizures Nausea and vomiting Focal motor or sensory impairments Papilledema Ataxia Hemiparesis
Cerebellar abscess - Nystagmus, ataxia, vomiting,
and dysmetria Brainstem abscess - Facial weakness, headache, fever, vomiting, dysphagia, and hemiparesis Frontal abscess - Headache, inattention, drowsiness, mental status deterioration, motor speech disorder, and hemiparesis with unilateral motor signs Temporal lobe abscess - Headache, ipsilateral aphasia (if in the dominant hemisphere), and visual defects
Causes
Anaerobic and microaerophilic cocci and gram-
negative and gram-positive anaerobic bacilli are the most important isolates. A high number of brain abscesses are polymicrobic. The predominant organisms include the following:
– Staphylococcus aureus – Aerobic and anaerobic streptococci (especially Streptococcus intermedius) – Bacteroides, Prevotella, and Fusobacterium species – Enterobacteriaceae organisms – Pseudomonas species – Other anaerobes
Investigations
Routine
CSF
Imaging – MRI
Treatment
Medical
Surgical
Encephalitis
Introduction
Encephalitis, an inflammation of the brain
parenchyma, presents as diffuse and/or focal neuropsychological dysfunction. From an epidemiologic and pathophysiologic perspective, encephalitis is distinct from meningitis, though on clinical evaluation the 2 often coexist with signs and symptoms of meningeal inflammation, such as photophobia, headache, or a stiff neck.
Cerebritis describes the stage preceding
abscess formation and implies a highly destructive bacterial infection of brain tissue Acute encephalitis is most commonly a viral infection with parenchymal damage varying from mild to profound
Pathophysiology
Portals of entry are virus specific. Many viruses are transmitted by humans, although
most cases of HSE are thought to be reactivation of the herpes simplex virus (HSV) lying dormant in the trigeminal ganglia. Mosquitoes or ticks inoculate arbovirus, and rabies virus is transferred via animal bite. With some viruses, such as varicella-zoster virus (VZV) and cytomegalovirus (CMV), an immunocompromised host is a key risk factor.
In general, the virus replicates outside the CNS
and gains entry either by hematogenous spread or by traveling along neural (rabies, HSV, VZV) and olfactory (HSV) pathways. The etiology of slow virus infections, such as those implicated in the measles-related subacute sclerosing panencephalitis (SSPE) and progressive multifocal leukoencephalopathy (PML), is poorly understood.
Once across the blood-brain barrier, the
virus enters neural cells, with resultant disruption in cell functioning, perivascular congestion, hemorrhage, and inflammatory response diffusely affecting gray matter disproportionately to white matter
Clinical features
The general viral prodrome is several days long
and consists of fever, headache, nausea and vomiting, lethargy, and myalgias. The specific prodrome in VZV, EBV, CMV, measles, and mumps includes rash, lymphadenopathy, hepatosplenomegaly, and parotid enlargement. Dysuria and pyuria are reported with St Louis encephalitis. Extreme lethargy has been noted with WNE
The classic presentation is encephalopathy with
diffuse or focal neurologic symptoms, including the following:
– Behavioral and personality changes, decreased level of consciousness – Stiff neck, photophobia, and lethargy – Generalized or localized seizures (60% of children with California encephalitis [CE]) – Acute confusion or amnestic states – Flaccid paralysis (10% with WNE)
The signs of encephalitis may be diffuse or focal
(80% of patients with HSE present with focal findings) as follows: Altered mental status and/or personality changes (most common) Focal findings, such as hemiparesis, focal seizures, and autonomic dysfunction Movement disorders (St Louis encephalitis) Ataxia Cranial nerve defects
Dysphagia (Rabies may account for
foaming at the mouth and hydrophobia.) Meningismus (less common and less pronounced than in meningitis) Unilateral sensorimotor dysfunction
Causes
The etiology of encephalitis is usually
infectious, but may be noninfectious, such as the demyelinating process in acute disseminated encephalitis. Infectious etiologies: Viral agents, such as HSV type 1 and 2 (almost exclusively in neonates), VZV, EBV, measles virus (PIE and SSPE), mumps, and rubella are spread through person-to-person contact.
Important animal vectors include mosquitoes,
ticks (arbovirus), and warm-blooded mammals (rabies, lymphocytic choriomeningitis). Bacterial pathogens, such as Mycoplasma species and those causing rickettsial or catscratch disease, are rare and invariably involve inflammation of the meninges out of proportion to their encephalitic components. Encephalitis due to parasites and fungi other than Toxoplasma gondii.
Investigations
Routine
CSF polymerase chain reaction (PCR): A PCR for
DNA HSV is 100% specific and 75-98% sensitive within the first 25-45 hours. Viral serology: Complement fixation antibodies are useful in identifying arbovirus Imaging EEG
Treatment
Supportive With the important exceptions of HSE and
varicella-zoster encephalitis, the viral encephalitides are not treatable beyond supportive care. The goal of treatment for acutely ill patients is administration of the first dose or doses acyclovir with or without antibiotics or steroids as quickly as possible.
Herpes Simplex Encephalitis
Introduction
HSE occurs as 2 distinct entities. – In infants, children, and adults, HSE is usually localized to the temporal and frontal lobes and is caused by herpes simplex virus type 1 (HSV1). – In neonates, however, brain involvement is more often diffuse, and the usual cause is herpes simplex virus type 2 (HSV-2), which is acquired at the time of delivery.
Pathophysiology
Brain involvement is diffuse, and petechial
hemorrhage and necrosis are distributed in an asymmetric fashion throughout the medial temporal and inferior frontal lobes. Involve direct virus-mediated and indirect immune-mediated processes.
AGE : HSE has a bimodal distribution by
age, with 1 peak occurring in those younger than 20 years and 1 occurring in those older than 50 years
Clinical features
Generalized
Focal
Investigations
Routine
CSF- PCR: Investigation of choice
Imaging : MRI EEG
Treatment
Acyclovir – 10 mgm/ kg hourly for 14-21
days
Neurosyphylis
Introduction
Syphilis (from the Greek word syphlos,
meaning crippled or maimed)
Pathophysiology
Syphilis is a sexually transmitted disease
caused by Treponema pallidum. Human beings are the only host. Treponemes are spirochetes, which are thin, delicate, helically coiled organisms measuring 5-20 micrometers in length.
Syphilitic infection of the nervous system
results in the most chronic insidious meningeal inflammatory process known. Invasion of the CNS occurs early in the course of untreated syphilis
Clinical features
Symptoms of neurosyphilis, principally of central
origin, include the following in order of frequency: Personality change - 33% Ataxia - 28% Stroke - 23% Ophthalmic symptoms (eg, blurred vision, reduced color perception, impaired acuity, visual dimming, photophobia) - 17% Urinary symptoms (eg, bladder incontinence) 17%
Lightning pains - 10%
Headache - 10%
Dizziness - 10% Hearing loss - 10% Seizures - 7%
Signs of neurosyphilis, in order of decreasing
frequency, include the following: Hyporeflexia - 50% Sensory impairment (eg, decreased proprioception, loss of vibratory sense) - 48% Pupillary changes (anisocoria, Argyll Robertson pupils) - 43% Cranial neuropathy - 36% Dementia, mania, or paranoia - 35%
Romberg sign - 24%
Charcot joint - 13%
Hypotonia - 10% Optic atrophy 7%
Neurosyphilis is divided into 2 general categories:
(1) early involvement of the CNS limited to the meninges and (2) parenchymal involvement. The 6 delineated groups are as follows:
– – – – – – Asymptomatic Acute syphilitic meningitis Meningovascular syphilis Tabes dorsalis (parenchymal) General paresis (of the insane [GPI]) Optic atrophy
Investigations
VDRL and rapid plasma reagin (RPR) are
nontreponemal tests, whereas FTA-ABS and microhemagglutination assay-T pallidum (MHA-TP) are treponemal tests.
Treatment
neurosyphilis (HIV negative) This treatment group includes patients with
late latent disease (>1 y) and those in whom CSF was not examined in latency.
– `Benzathine PCN G - 7.2 million units IM in doses of 2.4 million units at 7-day intervals, over 15 days – Aqueous benzyl PCN G or procaine PCN G Total of 9 million units IM in doses of 600,000 units daily over 15 days
Symptomatic neurosyphilis or asymptomatic
neurosyphilis (HIV positive) Either of the following is acceptable.
– Aqueous (crystalline) PCN G - 2-4 million units IV every 4 hours for 10-14 days (some consider adding oral PCN to supplement levels) – Procaine PCN G - 2.4 million units IM daily plus probenecid 500 mg PO qid for 10-14 days (probenecid increases brain concentrations of PCN less than it increases CSF concentrations)
Poliomyelitis
Introduction
Poliomyelitis is an enteroviral infection that
can manifest in 4 different forms:
– – – – inapparent infection, abortive disease, nonparalytic poliomyelitis, paralytic disease.
Pathophysiology
Poliovirus is an RNA virus that is transmitted
through the oral-fecal route or by ingestion of contaminated water. Three serotypes are able to cause human infection. The incubation period for poliovirus is 5-35 days. The viral particles initially replicate in the nasopharynx and gastrointestinal tract and then invade lymphoid tissues, with subsequent hematologic spread. After a period of viremia, the virus becomes neurotropic and produces destruction of the motor neurons in the anterior horn and brainstem.
The destruction of motor neurons leads to
the development of flaccid paralysis, which may be bulbar or spinal in distribution
Clinical features
In cases of abortive poliomyelitis (5-10%),
a history of the following is found with normal neurologic examination findings: Anorexia Vomiting Abdominal pain Duration of illness usually less than 5 days
When nonparalytic poliomyelitis develops,
symptoms usually are those observed in abortive disease in addition to meningeal irritation. Paralytic poliomyelitis involves systemic manifestation, such as respiratory failure, in addition to symptoms observed in nonparalytic poliomyelitis.
Patients who have recovered from
poliomyelitis occasionally develop a postpoliomyelitis syndrome, in which recurrences of weakness or fatigue are observed and which usually involve groups of muscles that were initially affected. This postpolio syndrome may develop 20-40 years after infection with poliovirus.
The spectrum of disease varies from inapparent
infection to paralytic disease. In mild cases, the following nonspecific signs and symptoms are observed and usually resolve within a few days:
– – – – – – Fever Headache Nausea Vomiting Abdominal pain Oropharyngeal hyperemia
Nonparalytic poliomyelitis is characterized
by the symptoms described above in addition to the following:
– – – – Nuchal rigidity More severe headache Back and lower extremity pain Meningitis with lymphocytic pleocytosis (usually)
Paralytic poliomyelitis occurs in fewer than 5% of
affected patients and is characterized by the following:
– Compromise of the motor neurons may be localized or widespread. – More frequently, asymmetric loss of muscle function is observed with involvement of major muscle groups. – Muscle atrophy is generally observed several weeks after the beginning of symptoms. – Recovery may be complete, partial, or absent.
Investigations
A 4-fold increase in the immunoglobulin G
(IgG) antibody titers or a positive antiimmunoglobulin M (IgM) titer during the acute stage is diagnostic.
Treatment
Supportive
Chorea
Introduction
Chorea is defined as brief, irregular,
unpredictable, purposeless movements that flow from one body part to another without a rhythmic pattern. The term chorea is derived from the Greek word for dancing and was applied initially to epidemics of dancing mania in the Middle Ages, in which large numbers of people danced together for days
Causes
Inherited – Ataxia-telangiectasia – Benign hereditary chorea – Hereditary spinocerebellar ataxias – Huntington disease – Inborn errors of metabolism
Drugs – Anticholinergics – Anticonvulsants (eg, phenytoin, carbamazepine, phenobarbital) – Antidopaminergic agents (eg, phenothiazines, haloperidol, metoclopramide) – Antihistamines – CNS stimulants (eg, amphetamines, methylphenidate, pemoline) – Dopamine agonists (eg, levodopa, pergolide) – Lithium – Oral contraceptives
Endocrine – Hyperthyroidism – Chorea gravidarum – Hypoparathyroidism, pseudohypoparathyroidism
Immune/infectious – Behçet disease – Other infections - Pertussis, diphtheria, varicella – Sydenham chorea – Systemic lupus erythematosus – Bacterial endocarditis – Herpes simplex encephalitis – HIV related – Infectious mononucleosis – Mycoplasmal pneumonia – Viral meningoencephalitis (eg, mumps, measles, varicella)
Metabolic – Hypocalcemia – Hypoglycemia and hyperglycemia – Hypomagnesemia – Hyponatremia, hypernatremia, and central pontine myelinolysis – Renal failure
Sydenham’s chorea
Chorea typically occurs in about 10-20% of
patients with acute rheumatic fever. SC is a major manifestation of acute rheumatic fever. With the 1992 modifications of the Jones criteria, SC alone is sufficient to make the diagnosis of a first attack of acute rheumatic fever. SC often presents with other rheumatic fever manifestations during the acute episode, although an isolated form characterized by chorea alone has been described.
Clinical features
The main features of SC are involuntary
movements, hypotonia, and muscular weakness. Chorea can be generalized or unilateral, predominantly involving the extremities and face. Movements occur at rest and are exacerbated by stress; they disappear during sleep.
Treatment
Valproic acid at a dose of 15-20 mg/kg/day has
been reported to control choreic movements within 1 week. Carbamazepine, may have a similar effect. Diazepam in nonsedative doses also may be used. Dopaminergic blockers (pimozide and haloperidol) and depletors have been used widely, but they have significant side effect profiles. Pimozide has fewer side effects than haloperidol, and in low doses pimozide has a lower risk of tardive dyskinesia
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