Meningitis and Encephalitis Flashcards
Bacterial meningitis epidemiology? Etiology? Pathophysiology ?
Incidence —> 5-10 cases/100.000 person/year. They are most common in extreme age categories, in elderly and newborns. The most frequent etiology of bacterial meningitis is S. pneumoniae (49%), and the second most common cause is N. meningitidis (34%).
Pathophysiology —> Microorganisms penetrate the subarachnoid space through : Hematogenous spread -> most frequent route of diffusion, direct penetration (e.g. in presence of a wound), extension of nearby or contiguous infectious foci (e.g. infections in the nose or nasal sinuses), lymphatic peri-venous spread (less frequent). Regardless of the mechanism of entry, there will be bacterial replication in subarachnoid space and subarachnoid inflammation.
- Increased BBB permeability which leads to vasogenic edema.
- increased CSF outflow resistance which leads to hydrocephalus and interstitial edema.
- Cytotoxic edema.
- Cerebral vasculitis and or infarction.
Signs and symptoms of bacterial meningitis?
They depend on the patients age.
Infants —> symptoms include irritability, poor feeding, vomiting, respiratory systems, apnea. Signs include fever, lethargy, stupor, coma, seizures, petechial or purpuric rash.
Children and adults —> symptoms include headache, neck stiffness, unconsciousness, photophobia, respiratory problems. Signs include fever, lethargy, coma, focal neurological deficits, seizures, cranial nerve palsies, petechial or purpuric rash.
Neisseria meningitidis in meningitis?
It is a gram negative diplococci, often found intracellularly which causes acute cloudy/prurulent CSF meningitis. It is the second most common cause of meningitis and commonly affects young children especially those who go to school, clubs or gym.
Risk factors include complement deficiency which predisposes to infection.
It is transmitted via inter human spread through salivary particles.
Serotypes B and C are most virulent and only B accounts for 50% of sporadic cases. A and C are more frequent during outbreaks.
Clinical features include meningitis symptoms, meningococcal septicemia suspicions like purpuric rash, DIC and Waterhouse friderichsen syndrome.
Complications include CN deficits, brain infractions, cognitive disabilities and hydrocephalus, these all occur in 10-20% of cases.
Lethality related to sepsis is 30% and 6-12% related to late recognition.
Chemoprophylaxis for close contact must be given within 24h and it include : ciprofloxacin 500mg single dose, ceftriaxone 250mg single dose, rifampicin 600mg every 12h for 2 days.
Streptococcus Pneumoniae in meningitis?
Gram positive diplococci causing cloudy/prurulent CSF meningitis. It is the first cause of bacterial meningitis in adults and usually affects older adults, >60 yr.
It is endemic and there are about 90 serotypes.
Risk factors include : otitis media, mastoiditis, sinusitis-immunosupression due to splenectomy, falciform anemia, B cell depleting therapies- alcohol abuse- DM- chronic kidney insufficiency- neurosurgery.
Remember to check for involvement of lungs, since Streptococcus pneumoniae meningitis has been associated to lobar pneumonia in elderly individuals.
Gram + sepsis : no rash, slower evolution than gram - sepsis, DIC is also less frequent.
It is common to see in patients leptomeningeal enhancement.
Sequelae include VIII CN deficit, II CN deficit, brain infarction, hydrocephalus.
Therapy include anti microbial therapy of ceftriaxone + vancomycin with addition of ampicillin if listeria is a concern. If patient is severely allergic to beta lactams choramphenicol can be used. Supportive therapy including fluid and electrolytes, monitoring for ICP and hydrocephalus.
Vaccinations for bacterial meningitis?
At this time, the recommended vaccinations are :
- Age 0-6 years : Anti-meningococcus B and C, Anti pneumococcus
- Adolescents : Anti-meningococcus (Quadrivalent A, C, W135, Y)
- Age > 65 years : Anti-pneumococcus
For risk categories, such as doctors or subjects who live in endemic zones for a certain pathogen, there might be further possibilities for free vaccinations.
Viral meningitis?
Incidence is 5-35/100.000 person year, it is the most frequent case of meningitis.
Etiology : The majority of cases are caused by enteroviruses, which account for 80% and include ECHO, Coxsackie, and Poliovirus, particularly in children. Paramyxoviruses, such as the epidemic parotitis virus, are responsible for about 10% of cases. Less frequently, herpesviruses (HSV-1/2, CMV, VZV, EBV, HHV6), retroviruses (HIV, HTLV-1), and arthropod-borne viruses (West Nile Virus, lymphocytic choriomeningitis virus) are implicated. Parvovirus B19 and other miscellaneous viruses are also rare causes.
Pathophysiology: Viral meningitis begins when a virus enters the body through mucosal surfaces, such as the respiratory or gastrointestinal tract, or the conjunctiva. After local replication, the virus causes primary viremia, which can lead to replication in end organs and CNS invasion. In some cases, a secondary viremia can occur years later, reactivating the infection and causing CNS involvement.
Clinical Presentation: Systemic symptoms include low-grade fever (typically lower than bacterial meningitis), anorexia, myalgia or arthralgia, and nausea or vomiting. Certain viruses may produce specific features, such as pharyngitis and diarrhea with enterovirus, abdominal pain with epidemic parotitis, or vesicles in the oropharynx with Coxsackievirus. Neurological symptoms include meningeal signs such as headache, nuchal rigidity, and photophobia. If untreated, the infection can progress to meningoencephalitis, with parenchymal lesions causing focal or generalized neurological deficits.
Differential Diagnosis: Viral meningitis can present acutely or subacutely, often with light-to-moderate symptoms, but occasionally with severe features. It must be differentiated from acute bacterial meningitis, subacute or chronic infectious meningitis, and encephalitis.
Diagnostic Tests: Diagnostic workup includes blood tests for routine parameters, inflammatory markers, and viral serologies. Cerebrospinal fluid (CSF) analysis with PCR is essential for identifying the viral pathogen, and a basal CT should be performed to exclude critical lesions before lumbar puncture. Contrast-enhanced MRI is also critical, as it can provide patterns specific to certain viral infections.
Treatment: Herpetic infections are treated with antiviral agents, such as acyclovir (10 mg/kg every 8 hours), as untreated cases can lead to death. HIV-related meningitis requires antiretroviral therapy. For other viral causes, treatment is primarily supportive, including hydration and analgesics. Steroids should not be used unless herpetic infections have been ruled out, as they may complicate the disease course.
Subacute/chronic meningitis?
Definition: Subacute and chronic meningitis refers to meningeal inflammation that develops gradually over days, weeks, or even months. Symptoms may be subtle, with recurrence occurring years after the primary infection. Diagnosis is challenging due to overlapping presentations with immune-mediated vasculitis or reactivated viral infections, often leading to delays in diagnosis and complications.
Etiology: Subacute/chronic meningitis can be caused by both infectious and non-infectious conditions. Infectious causes include viruses, Mycobacterium tuberculosis, Brucella (linked to unpasteurized milk), Leptospira (contact with animals or water), Amoebiasis, Borrelia (deer ticks), and syphilis. Non-infectious causes include neoplasms and immune-mediated conditions such as vasculitis or sarcoidosis. Patient history is critical in identifying these triggers.
Clinical Approach: A detailed history is vital, focusing on exposure to pathogens (e.g., TB, fresh dairy products, ticks, sexual transmission), travel and occupational history, and systemic diseases like pulmonary TB or sarcoidosis. The physical exam should assess general, neurologic (meningeal signs, cranial nerves, focal deficits), thoracic (e.g., pneumonia), dermatologic (e.g., lesions), and ophthalmologic (uveitis, retinitis) findings.
Clinical Presentation: Symptoms are variable and systemic signs like fever, nausea, vomiting, and headache are often absent. Neurological signs include meningeal syndrome, encephalopathic features (altered mental status, seizures, focal deficits), and cranial nerve palsies.
Diagnostic Tests: Diagnosis relies on a combination of tests:
1. Blood tests: CBC, inflammatory markers, and serologies (e.g., ANA, ENA, Quantiferon).
2. CSF analysis: Identifies cell type (mononuclear cells with low glucose suggest TB or fungal infection, while eosinophils suggest parasitic causes). PCR and antibody/antigen assays help pinpoint the pathogen.
3. Imaging: MRI with contrast is sensitive, showing dural or leptomeningeal enhancement.
4. Chest X-ray and total-body CT/PET scans: Assess systemic infections or malignancy.
5. Biopsy: For definitive diagnosis in suspected malignancy or granulomatous diseases.
Differential Diagnosis: Based on CSF analysis, mononuclear cells with low glucose suggest TB or syphilis, normal glucose points to non-infectious causes, neutrophilic predominance suggests bacterial/fungal infections, and eosinophilia suggests parasitic or fungal etiologies.
Treatment: Management depends on the underlying cause. Infectious etiologies require targeted antimicrobials (e.g., antitubercular therapy for TB, antibiotics for syphilis), while non-infectious causes are treated with immunosuppressants. Early identification of the etiology is crucial to prevent irreversible complications.
Mycobacterium tubercolosis meningitis?
Mycobacterium tuberculosis is a gram-positive, alcohol- and acid-resistant bacillus that can cause subacute or chronic meningitis, often due to reactivation of a latent infection. It is an intracellular pathogen, which makes it difficult to clear, and is associated with high mortality, particularly in immunocompromised patients such as those with HIV.
Pathophysiology involves chronic inflammation, primarily at the base of the brain. The inflammatory exudate encases cranial nerves and blood vessels, leading to complications such as vasospasm, thrombosis, and ischemic lesions. Tuberculomas and miliary nodules may form, contributing to multifocal encephalitis. Granulomas can obstruct cerebrospinal fluid (CSF) drainage, resulting in hydrocephalus, which can present as either an acute complication or a chronic sequela.
Clinical features develop gradually over months. Early symptoms include chronic headache unresponsive to standard treatment, along with fever and behavioral changes. As the disease progresses, cranial nerve deficits and focal neurological signs emerge. Small-vessel strokes frequently occur in the brainstem, leading to conditions such as Weber syndrome, characterized by oculomotor nerve deficits on one side and contralateral hemiparesis. Hydrocephalus is another common complication caused by granulomas obstructing CSF pathways.
Diagnostic tests include analysis of cerebrospinal fluid, which often appears xanthochromic or colorless, with low glucose levels, increased mononuclear cells, elevated protein, and rich fibrinogen content. Ziehl-Nielsen staining can confirm the presence of acid- and alcohol-resistant bacilli. Post-contrast T1-weighted MRI is the most informative imaging modality, showing enhancement of the base of the brain. FLAIR imaging helps identify tuberculomas and miliary nodules, while hydrocephalus can be visualized through structural imaging.
Therapy requires a combination of antitubercular drugs, including rifampin, isoniazid, pyrazinamide, and ethambutol, often supplemented with dexamethasone to reduce inflammation and prevent complications like hydrocephalus or cranial nerve damage.
Differential diagnosis includes conditions that mimic tuberculosis meningitis, such as neuro-sarcoidosis, which presents with leptomeningeal enhancement and can be distinguished by chest X-ray. Secondary lymphoma and carcinomatous meningitis should also be considered; these conditions typically cause pachymeningitis and, in carcinomatous meningitis, involvement of cranial nerve VIII. Distinguishing between these conditions and tuberculosis meningitis relies on CSF analysis, imaging, and a detailed patient history.
What is encephalitis? Signs and symptoms? Classification?
Encephalitis is the inflammation of the brain parenchyma, most commonly caused by infections, with viruses being the predominant pathogens. Bacteria and fungi are less common causes. The two major forms of encephalitis are primary encephalitis, resulting from direct CNS invasion by pathogens, and secondary encephalitis, a post-infectious or autoimmune process involving immune-mediated damage to CNS structures.
Patients typically present with headache, neck stiffness, and fever, accompanied by confusion or altered consciousness. Other symptoms include vomiting, photophobia, and phonophobia. Focal neurological deficits, such as weakness or seizures, are common due to brain parenchymal involvement. Skin rash is usually absent, although clinical manifestations vary depending on the etiology.
Classification : based on etiological agent such as viruses, bacteria, fungi, Protozoa- based on pathogenic mechanism so primary or secondary encephalitis- disease course so acute, subacute or chronic- localization so nervous tissue polioencephalitis (grey matter), leucoencephalitis (white matter), or panencephalitis (both grey and white matter) and anatomical site hemispheres, brainstem, cerebellum, spinal cord, meninges.
Viral encephalitis causes?
They can be caused by direct or indirect pathogenic mechanisms and DNA/RNA viruses .
DNA viruses : Herpes virus like HSV 1, HHV6, CMV, EBV - papovavirus - poxvirus - adenovirus.
RNA viruses : enterovirus, togavirus, rhabdovirus, retrovirus, orthomyxovirus and others.
Non viral encephalitis causes?
Bacteria like streptococci, legionella, listeria, brucella, salmonella.
Rickettsiae like prowazeki, rickettsii, tsutsugamushi.
Fungi like aspergillus, candida.
Spirochetes like treponema and leptospira.
Protozoa like plasmodium, toxoplasma, trypanosoma.
Clinical presention, diagnostic tests, DDX and treatment of encephalitis?
Clinical Presentation : Encephalitis presents with a combination of general inflammatory symptoms, neurological symptoms, and in some cases, signs of involvement in other organ systems. General symptoms include fever, asthenia, and myalgia. Neurological symptoms may be diffuse or focal. Diffuse symptoms include altered consciousness (ranging from confusion to coma), generalized seizures, myoclonus, intracranial hypertension, and meningeal signs. Focal symptoms vary depending on the brain region affected and may include partial seizures with secondary generalization, focal deficits, and cognitive or psychiatric disturbances.
Diagnostic Tests : EEG is a critical tool in suspected encephalitis cases, helping to distinguish focal from generalized encephalopathy. For example, in herpes simplex virus encephalitis, EEG shows periodic lateralized epileptiform discharges originating from the temporal lobes. In Japanese encephalitis, there is diffuse slowing without focal abnormalities, indicating illness severity. Laboratory tests include routine blood work, culture of body fluids, IgM antibody detection, and PCR for pathogen identification. Imaging is essential, with MRI being the most sensitive modality. MRI sequences like DWI and post-contrast FLAIR detect early lesions and leptomeningeal enhancement. CSF examination is a cornerstone of diagnosis, showing pleocytosis in over 95% of cases, though up to 10% of viral encephalitis cases may have normal CSF findings.
Differential Diagnosis : The differential diagnosis includes meningitis, cerebrovascular diseases, brain tumors, metabolic or toxic encephalopathies, paraneoplastic or autoimmune encephalitis, and psychiatric disorders. Distinguishing encephalitis from these conditions relies on a combination of clinical presentation, imaging, EEG, and CSF analysis.
Treatment: involves both specific and symptomatic therapies. Viral encephalitis is managed with antivirals like acyclovir, while non-viral encephalitis requires appropriate antimicrobial agents. Symptomatic therapies include antiepileptic drugs for seizure control and anti-edema drugs, such as osmotic diuretics, in cases of brain herniation. Supportive care, including hydration and maintenance of vital functions, is crucial for managing critically ill patients. Early diagnosis and targeted treatment are essential to minimize complications and long-term neurological deficits.
Herpes simplex encephalitis?
Epidemiology : HSV encephalitis has an incidence of approximately 2.2 cases per million people per year.
Primarily affecting young individuals between 5–30 years and older adults over 50 years. HSV-1 is the most common causative pathogen in adults and children, while HSV-2 is more common in neonates.
Neuropathology : The condition is characterized by bilateral necrotic or necrotic-hemorrhagic lesions primarily in the temporal and fronto-basal brain regions. Without timely recognition and treatment, these lesions lead to significant brain parenchymal destruction. Eosinophilic nuclear inclusions, known as type A Cowdry bodies, are observed in neurons and glial cells.
Pathogenesis : In the majority of cases (70%), HSV encephalitis results from reactivation of HSV-1, which propagates to the CNS via the olfactory tract or trigeminal nerve. In the remaining 30%, it is caused by primary HSV-1 infection, most often in individuals under 18 years of age.
Clinical Features : The onset is typically insidious, with early symptoms such as memory deficits and hallucinations. Patients may exhibit focal neurological deficits, including cranial nerve involvement, hemiparesis, dysphasia, or ataxia. Altered mental status and psychiatric symptoms, such as behavioral changes, hypomania, or amnesia, are common due to temporal lobe involvement. Seizures, particularly originating from the temporal uncus, are frequently observed, as the hippocampus is a highly epileptogenic region. More than 90% of patients present with one of these symptoms accompanied by low-grade fever (37–37.5°C). The disease course can be aggressive, with intracranial hypertension and temporal lobe involvement leading to uncal herniation in up to 30% of cases, manifesting as mydriasis due to cranial nerve III compression. Long-term sequelae may include residual epilepsy, personality changes, and memory deficits, and recurrence occurs in 5% of cases.
Diagnosis : EEG findings always show abnormalities localized to the temporal and fronto-basal regions. MRI reveals hyperintensity on FLAIR images with diffusion-weighted imaging (DWI) restriction, indicative of early lesions, which may undergo hemorrhagic transformation within days if untreated. CSF analysis, performed only when brain herniation is excluded, typically reveals increased pressure, pleocytosis (10–20,000 cells/μL), elevated erythrocyte counts (particularly in hemorrhagic cases), and increased IgG protein levels. PCR detection of HSV DNA in CSF is definitive for diagnosis.
Treatment: The primary treatment is intravenous acyclovir at a dose of 10 mg/kg three times daily for 10–14 days. An alternative or adjunctive therapy is vidarabine at 15 mg/kg daily via continuous intravenous infusion over 12 hours. Supportive therapies include antiepileptic drugs for seizure control and measures to manage complications. Early initiation of antiviral therapy is critical to prevent fatal outcomes or severe neurological sequelae.
West Nile encephalitis?
Etiology : West Nile encephalitis is caused by the West Nile virus, a mosquito-borne flavivirus. While most infections are asymptomatic, certain factors increase the risk of the neuro-invasive form, including advanced age, malignancies, and organ transplantation.
Clinical Manifestations : The majority of infections are asymptomatic, but about 20% of patients develop West Nile fever within two weeks of infection. This is typically a self-limited illness often accompanied by a skin rash in 50% of cases. Neuro-invasive disease occurs rarely but is severe, with a mortality rate of approximately 10%. Clinical manifestations of the neuro-invasive form are diverse and include encephalitis, extrapyramidal symptoms (often associated with cognitive deficits), and acute flaccid paralysis syndrome, which frequently leaves patients with residual motor deficits. Involvement of the peripheral nervous system is less common.
Diagnosis : MRI findings in neuro-invasive disease may show T2 hyperintensity in regions such as the basal ganglia, thalami, caudate nuclei, brainstem, and spinal cord, reflecting areas of inflammation. EEG typically reveals generalized continuous slowing, more prominent in the frontal and temporal regions.
Treatment : Currently, there are no specific antiviral therapies or vaccines available for humans. Treatment is limited to supportive care, focusing on managing symptoms and complications.
Non infectious encephalitis?
Definition and Pathophysiology : Non-infectious encephalitis is a rapidly progressive encephalopathy, typically developing within six weeks, caused by brain inflammation due to autoimmune mechanisms. It is driven by autoantibodies targeting the CNS.
These autoantibodies are classified into three groups : those against surface antigens (e.g., NMDA receptor), which are often paraneoplastic but pathogenetic and associated with better recovery; those against intracellular synaptic proteins (e.g., GAD65), which have an intermediate prognosis; and those against intracellular antigens (e.g., Hu), which are typically non-pathogenic, paraneoplastic, and associated with poor prognosis. This condition can be the first manifestation of an underlying tumor, such as small cell lung carcinoma, testicular seminoma, or thymoma.
Clinical Features : The hallmark clinical features include subacute onset of working memory deficits, altered mental status, or psychiatric symptoms.
Graus’s criteria for possible autoimmune encephalitis require all three: subacute onset, seizures unexplained by a prior disorder, and suggestive MRI or CSF findings. Neurological symptoms include seizures, personality changes, and focal deficits. Some forms, like limbic encephalitis, present with bilateral T2W abnormalities in the medial temporal lobes. Anti-NMDA receptor encephalitis, common in young women and often paraneoplastic (e.g., ovarian teratomas), progresses through stages starting with prodromal symptoms like fever and headache, followed by confusion, memory deficits, and later seizures, movement disorders, and autonomic instability. Early recognition and tumor removal are critical to reversing symptoms before irreversible damage occurs.
Diagnosis : involves identifying the target autoantigen through serum and CSF analysis, imaging, and antibody detection. MRI findings often show bilateral medial temporal lobe abnormalities, while CSF analysis may reveal pleocytosis (>5 WBC/mm³). EEG may show slowing or epileptiform activity, helping differentiate autoimmune encephalitis from other conditions. Infectious causes must be excluded before confirming autoimmune etiology.
Treatment:
Treatment begins with addressing any associated tumors. First-line therapy includes IV methylprednisolone (1 g/day for 3–5 days, followed by tapering) and/or IV immunoglobulins (IVIg) (0.4 g/kg/day for 5 days). If the response is inadequate, second-line therapies like rituximab (anti-CD20 antibody, weekly for four weeks) or cyclophosphamide (750 mg/m² IV monthly) are used. Early intervention is essential to prevent irreversible damage, particularly in cases with medial temporal lobe involvement, which can lead to residual deficits such as seizures or cognitive impairments.
Anti NDMA receptor encephalitis?
This specific form of autoimmune encephalitis is caused by antibodies against the NMDA receptor’s GluN1 subunit. It predominantly affects young individuals, especially women, and is often associated with ovarian teratomas or carcinomas. Symptoms evolve progressively, beginning with fever and headache and advancing to confusion, memory deficits, language impairment, seizures, and autonomic instability. Early diagnosis and treatment, including tumor removal, significantly improve outcomes, although delayed cases may lead to permanent brain atrophy and residual neurological deficits.
