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Dr Sadik AL-Ghazawe MRCP FRCP UK

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Infections of the nervous system

Bacterial infections

.Meningitis

.Suppurative encephalitis

.Brain abscess

.Paravertebral( epidural) abscess

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.Tuberculosis

.Leprosy (peripheral nerves.

.Neurosyphilis

.Diphhtheria(peripheral nerves)

.Tetanus(motor cells)

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Viral infections

.Meningitis

.Encephalitis

.Transverse myelitis

.Progressive multifocal leucoencephalopathy

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.Subacute sclerosing panencephalitis(late sequel).

.poliomyelitis

.Rabies

.HIV infection

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PRION DISEASE

.Creutzfeldt-Jakob disease

.Kuru

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Protozoal infections

.Mlaria

.Toxiplasmosis in immunsupressed

.Amoebic abscess

.

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Helminthic

.Schistosomiasis(spinal cord)

.Hydatid disease

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Fungal infections

.Candida meningitis

.Brain abscess

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MENINGITIS

Is a syndrome of fever, headache, and

meningismus with inflammation in the

subarchnoid space as evidence by CSF

pleocytosis.

.

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Note

Meningismus,

(1- headache 2-photophobia 3- neck stiffness)

Accompanied by other signs of meningeal irritation(Kernigs sign)

Meningismus is not specific to meningitis can occur in SAH.

Severity of clinical features varies according to causative organism, presence of other features such as skin rash

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Causes of meningitis

-Bacteria

Viruses

.Entroviruses

.Mumps

.Infuenza

.Herpes simplex

.Varicella zoster

.HIVEpstein-Barr

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Protozoa and parasites

.

.Amoeba

.Toxoplasma

Fungal

.Candida

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Non-infective(sterile)

.Malignant disease

.Breast,Bronchial cancer

.Leukaemia

.Lymphoma

Inflammatory disease

SLE ,Sarcoidosis ,Bejeget

aaa15A

Acute meningitis ,

1-presents within hours to days .

2-infectious with bacterial or viral cause.

3-DD OF NONINFECTIOUS ETIOLOGY

4-morbidity & mortality of bacterial meningitis is substantial.

5-importance of prompt recognition & management of potential cause.

Chronic meningitis,

Longer than 4 wk duration

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Predisposing factors:

1- environmental factors (overcrowding, poverty).

2-Host factors,

A- immunoglobulin deficiency.B-Sickle cell disease.C-alcholism.D-Diabetes.

Note Infections of mixed aetiology may occur following head injury, mastoiditis or iatrgenically after LP.

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❖Bacteria may invade the subarachnoid space

❖directly by spread from contiguous structures,

❖ e.g. sinuses, or more commonly, indirectly from the blood steam.

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Causative organisms

In neonates

Gram –ve bacilli,e.g.- E.coli,- Klebsiella.-Haemophilus influenzae.

AB ,ampicilin with ceftriaxone

In children-Haemophilus influenzae-Pneumococcus(Strep.pneumoniae)-Meningococcus (Neisseria meningitides)

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In adults

Pneumococcus.

Meningococcus

Other bacteria-Streptococcus Pyogenes,

Staphylococcus aureus.

Host factors

❑Congenital,❑AID,❑Hyposplenism,❑ Alcoholism

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Clinical features

The classical clinical triad is fever, headach and neck stiffness.

Prodromal features (variable)

A respiratory infection, otitis media, pneumonia associated with muscle

pain, backache and lethargy.

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Meningitic symptoms

Sever frontal/occipital headache, stiff neck, photophopia.

Systemic signs

High fever, transient purpuric or petechial skin rash in meningococcal meningitis.

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Meningitic signs

oNeck stiffness,

oKernig’s sign.

Associated neurological signs

❑ impaired conscious level

❑ Focal or generalized seizures are frequent(30%)

❑ Cranial nerve signs occur in 15% of patients.

❑ sensorineuronal deafness (not due to concurrent otitis media but to direct cochlear involvement)-20%.

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Focal neurological signs

hemiparesis,

dysphasia

hemianopia-occur in 10%.

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Non-neurological complication

1-Shock.

2-Coagulation disorders (thrombocytopenia,

3- disseminated intra vascular coagulation (DIC).

4-Inappropriate ADH secretion.

Septic complications:

Arthritis (direct infection or immune complex deposition)

Acute bacterial endocarditis.

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Features specific to causative bacteria

Haemophilus meningitis

➢ Generally occurs in small children.

➢ Preceding upper respiratory tract infection.

➢ Onset abrupt with a brief prodrome.

➢ Outcome, generally good. Less than 5% mortality

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Meningococcal meningitis

❑ Often occurs in epidemics where the organism is carried in the nasopharynx

❑ Septicaemia can occur with arthralgia ,purpuric skin rash.

❑ When overwhelming, confluent haemorrhages appear in the skin due to DIC.

❑ Gradual onset-good prognosis.

❑ Sudden onset with septicaemia-poor outcome.

❑ Overall mortality-10%.

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Complication of meningococcal septicaemia

1-meningitis2-rash3-shock4-DIC5-Renal failure6-peripheral gangrene7-Arthritis(septic ,reactive)8-pericarditis(septic, reactive)

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Pneumococcal meningitis

Predominantly an adult disorder.

Usually associated with debilitation, e.g. alcoholism.

May result from pneumonia, middle ear, sinus infection or follow splenectomy.

Onset may be explosive, progressing to death within a few hours.

Mortality-20% .

Poor prognostic signs-coma, seizures,low cell count in CSF.

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Investigations

1-If patient is in coma or has papilloedema or

focal neurological signs—exclude an intracranial mass with a CT

scan or MRI meningial inhancement .

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-Note , 1-If the patient is deteriorating rapidly,or has a bleeding

disorder that cannot be rapidly corrected,take off blood cultures

and commence Empirical antibiotics prior to scanning.

2-If above signs are absent or CT scan excludes a mass lesion-

--confirm diagnosis with a LP and identify the organism

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CSF Examination

Normal value

1-colour, crystal clear

2-Cells, less than 5 cells per cubic mm

3-Glucose 2.3-4.5 mmol per L 41-81 mg per Dl

4-Total protein 140-450mg per L 014-0.045 g per dL

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CSF examinationBacterial meningitis

1-moderate increase in pressure, less than 300mm.

2- CSF appearance slightly turbid to grossly purulent.

3-Gram stain of spun-down sediment:

Gram +ve paired cocci (pneumococcus).Gm –ve bacilli (haemophilus). Gm –ve intra and extracellular cocci

(meningococcus).

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4-Cell count is elevated,100-10000 cells/mm3 (80-90% polymorhponuclear leucocytes).

5-Glucose is depressed, CSF protein 100-500 mg /dL.

6-Enzyme lactic dehydrogenase is elevated.

7-CSF culture.

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Seriological/immunological tests

The polymerase chain reaction(PCR) in CSF & blood to identify

etiologocal agen e.g, bacterial (DNA).

Blood cultures• Organism isolated in 80% of cases of Haemohpilus meningitis.

• Pneumococcus and meningococcus in less than 50% of patients.

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Serum electrolytes

✓Important in view of the frequency of inappropriate antidiuretic (ADH)

✓ hormone secretion in meningitis.

✓ Detect the source of infection.

✓-CXR-pneumonia✓-Sinus XR –sinusitis✓-Skull XR-fracture.✓-Petrous views-mastoiditis

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Treatment

Once meningitis is suspected,Isoloation that is because in meningocal

meningitis organism might be carried out in nasopharynges.

1-Empirical treatment must commence immediately, often before identification of the causative organism.

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2-The empirical antibiotics must penetrate CSF

,be in appropriate bactericidal dosage and be

sensitive to causal organism once identified.

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Initial therapy (before organism identification)

1-Neonates (above 1 month)- ampicillin+ceftriaxone.

2-Children (under 5 years)ceftriaxone with vancomycin

3-Adultsceftriaxone with vancomycine

4- Immunocompromised patientampicillin+vancomycine with ceftriaxone.

Duration14 days

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Monitoring

➢ 1-In a deteriorating patient,➢

CT scan will exclude the development of

➢1-hydrocephalus, ➢

2- abscess ➢

3- subdural empyema

➢ NOTE In suspected sinus thrombosis ,MR venography may be required

➢ Remove any source of infection, e.g. mastoidectomy or sinus clearance .

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Chemoprophylaxis

In meningococcal meningitis the risk to

household contact is increased(500-800 x) and

chemoprophylaxis should be offered

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Vaccines

are also available in H influenzae.Children 2-15 mt should be routinely immunized against H. influenza.

Age 1-18 y against N meningitidis.65y against S pneumoniae.

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SteroidsRecent trials in

1-children suggest that adjunctive therapy with

steroids (Dexamethasone) improves outcome-this may be due to

reducing cytokines released when organisms are destroyed .

2-In adults benefit of steroids is less certain.

3 -In the critically ill, intensive supportive therapy may be required

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Meningitis/CSF shunts

Meningetic infection may follow ,

1-CSF drainage,

2-operations for hydrocephalus.NOTE

This may occur in the immediate postoperative period or be delayed for weeks or months .

There are clinical features features of raised ICP may coexist due to shunt blockage .

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1-Bacteraemia is invariable and blood cultures identify the

responsible organism-usually staphylococcus albus

2-The infection seldom resolves with antibiotic therapy

alone and shunt removal is usually required

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CNS TUBERCULOSIS

-TB is an infection caused in man by one of two mycobacterium :-1-Mycobacterium tuberculosis 2-Mycobacterium bovis.

-The disease involves the NS in 10% of TB patients

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TB MENINGITIS

❖A-This the commonest manifestation of tuberculous infection of the NS .

❖1-In children, it is usually results from bacteraemia following the initial phase of primary pulmonary tuberculosis.

❖2-In adult, it may occur many years after the primary infection.

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❖B-following bacteraemia, metastatic foci of

❖ infection lodge in: Meninges, cerebral or spinal tissue, choroids plexus

❖ C -Rupture of these encapsulated foci result in

❖ spread of infection into the subarachnoid space.

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❖D-In adults, reactivity of metastatic foci may

occur spontaneously or result from impaired immunity

(e.g. recent measles, alcohol abuse, administration of steroids)

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The clinical features of tuberculosis meningitis (TBM) result from:

➢ Infection

➢ Exudation-which may obstruct the basal cisterns and result in hydrocephalus.

➢ Vasculitis –secondary to inflammation around vessels, resulting in infarction of brain and spinal cord.

➢ (The basal meninges are generally most severely affected.)

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Clinical features

➢- The majority of patients are adults.

➢- Childhood TBM is now rare.-➢

Non-specific prodromal symptoms develop over 2-6 wks.

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Staging :- useful for predicting outcome

➢Stage 1(early)—non specific symptoms,fever(80%),lethargy.

➢-Stage 2(intermediate)—confusion, cranial nerve

paralysis, meningism, Vasculitis (hemi paresis),

quadriparesis, ataxia, dysartheria.

➢Stage 3(advanced)—coma

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Complications.

➢Seizure may occur at the onset.

➢Involuntary movements (chorea, myoclonus) occur in10%.

➢Atypically the illness may develop slowly overmonths.

presenting with dementia or rapidly like pyogeni c (bacterial) meningitis.

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➢Note

1-Meningitis Occasionally cerebral features prevail rather than signs of meningitis

➢2-Untreated, the illness may progress from phase-1 to death over 3 wks period.

➢3-Arachnoiditis inflammatory exudates may result in hydrocephalus/dementia/blindness.

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•General investigations •Bacterial meningitis

➢anaemia, leucocytosis ,hyponatraemia (inappropriate ADH).

CSF

➢ 1- in acute cases polymorphn cells may predominate-500/mm3(50-4000/mm3).

➢2-The protein is elevated -1-5g/l.

➢3-The glucose level is usually less than 2/3 of simultaneously measured blood glucose.

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➢Investigations

➢CSFMicroscopy (Ziehl Neelson stain) reveals acid-fast

in 20% of patients.

➢CSF culture(6 weeks in Lowenstein-Jensen medium) should confirm the diagnosis.

➢Polymerase chain reaction (PMR) is increasingly available for the detection of bacterial DNA

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Investigations➢ CXR reveals changes of old or recent TB in50-70% of adults and 90% of children .

➢PPD skin test (tuberculin) : positive to intermediate strength in 60% .

Patients developing TBM while on steroids or with

recently acquired primary TB may give a negative response.

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➢CT/MRI: Shows 1- meningeal enhancement on basal views,

2-Ventricular enlargement, associated with

infarction and tubeculomas in10%.

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Diagnosis

➢ Based on

The clinical presentation with characteristics features .

➢ Even if Z.N stain is ve-,in view of progressive disease course,

Do not

➢ await the results of cultures before starting treatment

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Differential diagnosis of sub acute/chronic meningitis.

➢a-Viral meningoencephalitis (with normal CSF sugar).

➢b-Carcinomatous meningitis (with high CSF protein, low sugar).

➢c-Partially treated bacterial meningitis.

➢d-Fungal meningitis, sarcoidosis.

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TREATMENT

➢-If suspected,commence antituberculous treatment.

➢-Recommended treatment proramme:

➢Normal regime initiation phase 2mt

oIsoniazid(300mg/d) with pyridoxine 50mg to reduce polyneurathy. oRifampicin(600mg/d) –oPyrazinamide(15-30mg/kg/d).oStreptomycin 1gm.

o7-12mth,INH,rifampicin .oResistanceo Amikacin and ethionamide,ethambutal 1,200 mg

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Drug resistance

suspected due to

➢1-Previous antitubeeculous therapy,e.g.➢2-3rd word countries.➢3-History of previous infection.

➢Added a forth drugs-streptomycine(1gm/d) or ethambutol(25mg/kg/d).

➢INH and pyrazinamide penetrate meninges well. ---Other drugs penetrate less well especially when the inflammation begin to settle.

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Side effects

➢-INH may produce peripheral neuropathy-protect with pyridoxine 50mg/d

➢-Ethambutol may produce optic atrophy-check color vision.

➢-Streptomycin may cause 8th CN damage (vertigo and deafness).

➢-Nausea, vomiting, abnormal liver function and skin rashes may occur with all ani-TB drugs.

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Steroid therapy

➢1-Many clinicians, combined anti TB therapy with steroids in the

➢ hope that these will minimize the risk of obstructive endarteritis and arachnoids adhesions.

➢2-Although benefit are uncertain, steroids are recommended in patients with:-

❖A-Deteriorating conscious level.

❖B-Progressive neurological signs.

❖C-Evidence of spinal block.

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The course of treated TB meningitis

Outcome is influenced by, 1-the patient age of the patient. ❖

2-general state health , ❖

3- timing of initiation of treatment and ❖

4-the development of arachnoiditis and vascular complications.

❖Note-Treatment in early stages is associated with a 10% mortality ,while in later stages with a 50% mortality .

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❖Of those who survive, neurological sequeale persistent 30%-

❖hemiplegia,hypothalamic/pituitary dysfunction, blindness, deafness, dementia and epilepsy.

❖Note❖-With treatment, CSF sugar quickly returns to

normal ,the cellular reaction gradually diminishes

over 3-4mths,the protein level may take a similar time to return to normal.

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Brain tuberculomas

➢1-May occur in cerebral hemispheres, cerebellum, or brain stem, with or without tuberculous meningitis.

➢2- produce a space –occupying effect.

➢3-Lesion may be single or multiple.

➢4-CT and MRI demonstrate lesions but appearances are not pathgnomonic.

➢5-Most resolve over a few weeks with anti-TB therapy.

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Tuberculous meningomyelitis

1-Infection of leptomeninges results in an exudates that encases the

spinal cord and nerve roots.

2-Imaging may be normal while CSF shows 1- high protein, 2- lymphocytes and 3-rarely A.F bacilli.

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➢This disorder is now more frequent in AIDS patients.

D.D. includes❖cytomegalovirus, Cryptococcus, syphilis and lymphoma.

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Tuberculous meningomyelitis (cont)

1-Laminectomy and meningeal biopsy may be required to establish diagnosis.

2-When suspected, empirical theory with anti-TB drugs is appropriate.

The infection may result from :-

1-spread of intracranial infection.2- or direct spread from epidural infection.

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Tuberculous meningomyelitis (cont)

Clinical features

❖ 1-Ascending myelitis❖ 2-Root involvement/

3-Descending myelitis results in:-

1-weakness-(pyramidal and segmental). 2- root pain. 3- sensory loss. 4- sphincter disturbance.

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Tuberulous encephalopathy

➢-An autoimmune encephalopathy with features of-➢

1- acute allergic encephalomyelitis or ➢

2- haemorragic leukoencephalopathy. ➢

3- may complicate the course of T.B. infection

➢4-contribute significantly to the neurological sequelae .❖

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❖Clinically:-❖

1-convulsions.❖

2-deepening coma ❖

3- extensor posturing characterize this complication.

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Viral meningitis,encephalitis

1-Headach,fever,neck stiffness, patients donotappear as ill as those with bacterial meningitis.

2-Systemic viral infection may cause skin rash,

Lymphadenopathy,pleuritis,carditis and organomegly

.

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Viral encephalitis

Alteration of consciousness,seizures,focalneurological signs

Treatment, acyclovir.

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Heres simplex encephalitis

1-HSV typ 1(oral herpes) most common causeof sporadic fatal encephalitis.

2-Headah,neck stiffness,vomitimg,behavioraldisorder,

3-memory loss,hemiparesis,focal or genealizedseizures

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4-active herpes labialis is occasionally seen.

5-rabid progressive over several days,coma or death.

6-those who survived,memory loss, behavior changes.

7-CSF ,INCREASED PRESSURE,LYMPHOCYTOSIS.

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8-MILD protein elevation

DDBrain abscess

TreatementAcyclovir.

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Causes of chronic meningitis

1-infectiousPartial treated Bacterial,TB,syphillis,Lyme

disease,leptospirosia,Brucellosis.mycoplasma,HIV,

Fungal,parasitic,

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2-Non-infectios

Neoplastic meningitis,chemical meningitis,SAH,Sarcoidosis,Behcet syndrome,Wegener granulomatosis,Sjogern syndromes