Approach to a case of Fever with altered sensorium

A brief description about the possible d/d of fever with alteration of sensorium and how to approach the diagnosis through systematic yet focused history taking , physical examination and lab and radiological investigations.

1. Fever with altered sensorium Shilanjan Roy Dept Of Medicine Burdwan Medical College

2. Introduction A patient with fever and altered sensorium constitutes a medical emergency. Early recognition, efficient decision making and rapid institution of therapy can be life saving.

3. Levels of consciousness: Alert : Fully conscious Lethargic : Appear somnolent , but may be able to maintain arousal . Obtunded : Requires touch or voice to maintain arousal. Stuporous : Unresponsiveness from which the individual can be aroused only by painful stimulus . Comatose : State in which patient is unable to arouse or respond to noxious stimuli and is completely unaware of self and surroundings.

4. Fever with altered sensorium -- causes A. INFECTIONS Encephalitis Meningitis Cerebral malaria Brain abscess, subdural or epidural empyema Sepsis associated encephalopathy(SAE) Sepsis with DIC/TTP

5. Causes contd.. B. NON INFECTIOUS CAUSES OF FEVER a. OVERPRODUCTION OF HEAT : 1. Neuroleptic malignant syndrome 2. Malignant Hyperthermia. 3.Serotonin Syndrome 4.Cocaine, Amphetamine, ecstasy toxicity 5.Salicylate poisoning. 6.Thyrotoxic encephalopathy. 7.Convulsive status epilepticus . 8.Catatonic schizophrenia

6. b. IMPAIRED HEAT DISSIPATION 1.Anticholinergic toxicity e.g amitriptyline 2.Heat Stroke. c. STRUCTURAL LESIONS( IMPAIRED THERMOREGULATORY MECHANISM) 1.Hypothalamic lesion. 2.Brainstem lesion( stroke) 3.Intraventricular and subarachnoid haemorrhage d. MISCL. 1. ADEM(infectious or post infectious) 2.cerebral fat embolism 3.Altered sensorium with secondary cause of fever eg . Aspiration pneumonia in a stroke patient. ICH with Intra-ventricular extension

7. Important points: Presence of fever alone is not sufficient to make a diagnosis of an infectious etiology( e.g Meningitis or encephalitis) Encephalopathy may be precipitated by systemic infections or sepsis without cerebral inflammation ( septic encephalopathy ) Sepsis can lead to altered sensorium secondary to metabolic alterations like hypoglycaemia , hyperpyrexia, hypovolemia , hepatic or renal failure. Even in absence of infection there can be high rise of temp due to mechanisms such as overproduction or impaired dissipation of heat, non infectious CNS diseases, hypothalamic lesion.

8. Patients of NMS may have fever, neck stiffness, delirium, generalised rigidity, even after the offending drug has been withdrawn. WORLDWIDE , infection of the CNS is the commonest cause of Fever with altered sensorium . In a study from India among children < 18 yrs of age, commonest cause of acute febrile encephalopathy was VIRAL MENINGITIS , accounting for 40% of the cases. Among non viral, bacterial ( 34%), tubercular meningitis (7.9%) and cerebral malaria (5.2%) were most common .

9. Causes of infectious meningoencephalitis : A. VIRAL: a. DNA virus: 1. Herpes viruses: herpes simplex (HSV1,HSV2) other herpes viruses (HHV6, EBV, VZV, CMV) 2. Adenovirus. b. RNA viruses: Influenza, Polio, Entero , Measles, Rubella, Mumps, Rabies, Arbo , Reo, & Retrovirus

10. B. BACTERIAL: 1. Pyogenic meningitis 2. Mycobacterium tuberculosis 3. Mycoplasma pneumoniae 4. Listeria monocytogenes 5. Borrelia burgdorferri . 6. Tropheryma whippeli 7. Leptospira , 8. Brucella , 9. Legionella 10. Salmonella typhi .

11. C . RICKETTSIAL: Rickettsia rickettsii , R. typhi , R. prowazekii Coxiella burnetti D. FUNGAL: Cryptococcosis , coccidiomycosis , histoplasmosis , blastomycosis , candidiasis E. PARASITIC: Plasmodium, trypanosoma , Toxoplasma , Naegleria , schistosoma

12. APPROACH TO THE PATIENT HISTORY: Most important Sometimes only clue to correct diagnosis. Careful and systematic clinical assessment is key to management of a patient of febrile encephalopathy. Imp to differentiate infective vs non infective causes. Temporal course is also imp – whether fever preceded or followed altered sensorium or simultaneous. Classical triad of CNS inf – fever, neck rigidity, altered mental status . (present in majority of patients)

13. HISTORY: imp points: Onset of altered sensorium Headache Fever – grade/type Joint pain /rashes Nausea/ vomitting Contact with animals/dog bite Seizures – imp in children Focal deficits Geographical area Recent travel Drug addiction/use of antipsychotics Treatment with immunosuppressants /chemotherapy Trauma Recent illness/surgery Comorbidity such as diabetes

14. Physical examination: Thorough physical examination & neurological examination can provide imp clues to underlying aetiology . Skin rashes are common in meningo - coccal infn , rickettsial fever, VZV, colorado tick fever Parotitis in mumps Erythema nodosum may be a/w TB & histoplasmosis mucous membrane lesions common in Herpes virus infn , Upper resp tract infn favour Influenzae or Mycoplasma Look for lymphadenopathy , hepatosplenomegaly .

15. Detailed neurological examination including Pupillary size( anisocoria ) & reaction(loss) Forced eye deviation, Cranial nerve involvement, Decerebrate rigidity, Focal neuro deficit, Fundus examination for papilloedema help in diagnosis & planning investigations. Common focal abnormalities are Hemiparesis , Aphasia, Ataxia, Pyramidal Signs, Cranial Nerve Deficits, Involuntary Movements ( Myoclonus & Tremors), Partial Seizures & Papilloedema . warrant neuroimaging prior to LP Papilloedema Babinski sign

16. Signs of suspected meningitis: Kernig sign: flexing hip & extending knee – elicit pain in back n legs. Brudzinski sign: passive flexion of neck elicits flexion of hip Nuchal rigidity: severe neck stiffness. Jolt accentuation: exacerbation of existing headache with rapid head rotation

17. After getting clues from History and examination , investigations are tailored as per provisional diagnosis .

18. Investigations: BLOOD INVESTIGATIONS: TC, DC - CBC Coagulation profile Blood culture: + ve in 30-80% cases of bacterial meningitis. Serum CRP & Procalcitonin Blood biochemistry Arterial blood gases PBS: Relative lymphocytosis in viral meningitis. Leucopenia & thrombocytopenia – in rickettsial inf n & viral haemorrhagic fevers. For definitive diagnosis of malarial inf n P. falciparum gamet

19. CXR: May reveal changes suggestive of inf n such as Mycoplasma , Legionella , Tuberculosis LP: Always indicated when meningitis or meningoencephalitis is suspected. Includes: CSF pressure Gross examination for turbidity, cob web coagulum Colour Chemical examination: sugar, protein Cell count & cell types Microbiological examination: gram stain, india ink preparation, cultures PCR for tuberculosis, viral inf n Latex agglutination Limulus lysate assay

20. CSF findings Normal Viral Bacterial tubercular Fungal Opening pressure 60-180 mm of H 2 O Normal elevated Elevated/ variable Elevated/ variable Colour Clear Usually clear Turbid/ xanthochromic Xanthochromic /variable Clear/ variable TC <5cells/ cmm <100/ cmm >1000/ cmm Variable(100-500/ cmm ) Variable DC lymphocytes lymphocytes PMNs lymphocytes lymphocytes protein 20-40mg/dl N/ ed elevated elevated elevated Glucose 40-80mg/dl Usually normal decreased decreased decreased Microscopy Usually normal Gm stain + ve /variable AFB + ve India ink prepn

21. Neuroimaging : MRI CT scan Characteristic neuroimaging changes: Fronto temporal changes in HSV Thalamic & midbrain changes in Japanese encephalitis Basal exudates after contrast adm in TB Meningitis . Basal ganglia ring enhancing lesion in Toxoplasmosis . Multiple ring enhancing lesions in tuberculoma . TB meningitis HSV encephalitis

22. EEG: imp to rule out non convulsive status. d/d of focal encephalitis vs gene- ralised encephalopathy Characteristic EEG changes: Diffuse bihemispheric slowing in gen. encephalopathy Triphasic slow waves in hep encephalopathy. 2-3 Hz, periodic lateralised epileptiform discharges from temporal lobe in HSV.

23. Others: Thyroid function test Drug levels Urine toxicology screen

24. Patient with Fever and altered sensorium Precipitant known – drugs/toxins/heat Treat acc to cause Yes No C/F Sudden onset altered sensorium followed by fever Fever f/b altered sesorium (ac/ subac ./ chr ) 1 2 3 Fever f/b altered sesorium (course unclear) CT head Abnormal Normal Brain stem stroke, hypothalamic lesion & IVH/SAH Seizure, psychiatric features/ minimal MIS/ FD +/- MIS+++;FD +/- MRI brain/ CSF examintion / PBS CSF examintion / CT/MRI brain Encephalitis/ cerebral malaria Meningitis

25. Fever f/b altered sesorium (course unclear) MIS/FD/Imaging/ CSF MIS +++; FD+/-; Imaging +/- ; CSF+++ MIS +/-; FD ++; Imaging +++; CSF+/- MIS - ; FD - ; Imaging +/- ; CSF - Meningoencephalitis Structural lesion of brain Metabolic/ psychiatric / toxic 3

26. Suspicion of bacterial meningitis Immunocompromised state, papilloedema , focal nero deficits, delay in LP Blood culture & lumberpuncture stat Blood culture stat No Yes Dexamethasone + emperical antimicrobial therapy stat Dexamethasone + emperical antimicrobial therapy stat Negative CT Perform LP CSF suggesting of bacterial meningitis Continue / modify therapy Management algorithm for suspected bacterial meningitis

27. Evaluation of patient of febrile encephalopathy: Summary A. History: Fever, headache, vomitting , altered sensorium Geographical & seasonal factors Immune status, drug intake Contact with animals, insect bite, dog bite Foreign travel Occupation B. Clinical signs : Fever, neck stiffness, altered sensorium Kernig sign, Brudzinski sign, Jolt accentuation Skin & mucous membrane changes Lymph node, liver, spleen Other sites of concomitant inf n . Neurological exam n

28. C. Investigations: Blood: Urine: including myoglobinuria CXR : LP: Neuroimaging : EEG: In selected cases TFT Drug levels Urine toxicology screen D. management: Acc to cause

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