Neurological Presentations

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CHAPTER 3

Rapid assessment of patient Indications and Further reading, 25 with coma in the tropics, 19 contraindications for lumbar Classiﬁcation and further puncture in suspected CNS investigation of patients with infections,24 coma, 23

Neurological presentations are more common prevention are important. These may lead, in the tropics than in the developed industrial for example, to cysticercosis and typhoid. world. Infectious diseases make a major contri- • Immunosuppression, particularly as a result bution, but non-infectious causes are also im- of HIV, allows many other infections such as portant (Table 3.1). A complex mixture of cryptococcal and tuberculous meningitis. socioeconomic and environmental factors contribute to the increased incidence. Neurological syndromes Neurological diseases — particularly infections Reasons for increased incidence — can present with a range of syndromes. of neurological disorders in • Encephalopathy — a reduced level of con- the tropics sciousness from any cause (infectious, metabo- • Non-infectious neurological disorders — lic, vascular, traumatic). trauma is more common in the tropics, espe- • Meningism — clinical signs of meningeal irrita- cially road trafﬁc accidents. Patterns of vascular tion (headache, neck stiffness, Kernig’s sign; see disease are catching up with those in the devel- below). oped world, but the usage of drugs to control • Paralysis — weakness of one or more limb, res- them lags behind. piratory or bulbar muscles, which may be a • Infectious neurological diseases — the climate result of damaged upper motor neurones, supports transmission of insect-borne patho- lower motor neurones, peripheral nerves, or gens (malaria, trypanosomiasis, arthropod- muscles. borne viruses). Environmental factors include • Chronic neurological presentations — insidious the close proximity of homes to zoonotic infec- presentation over weeks or months, often with tions. Vaccine-preventable diseases are more changes in personality, behaviour or other psy- common (e.g. measles, tetanus, diphtheria, chiatric illness. Fever may not be prominent, polio). There is also unregulated use of over- even with an infectious cause (Table 3.2). the-counter antibiotics, leading to the partial • Headache — may be the only symptom (e.g. in pretreatment of central nervous system (CNS) cryptococcal meningitis). infections, which hampers diagnosis and thera- • Other focal neurological signs — including hemi- py, and promotes the development of antibiotic spheric signs, brainstem signs, seizures and resistance. movement disorders. •Poverty, overcrowding, poor sanitation and lack of education about disease risk factors and

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18 Chapter 3: Neurological Presentations

CAUSES OF NEUROLOGICAL DISEASE

Vascular Endemic/murine/flea-borne typhus (R. Ischaemia/infarct typhi/R. mooseri) Subarachnoid/subdural/extradural/ Scrub typhus (O. tsutsugamushi) intracerebral haemorrhage Rocky Mountain spotted fever (R. rickettsii) Hypertension/hypotension Fungi Cryptococcosis Infectious Histoplasmosis Direct effect on CNS Aspergillosis Bacteria Coccidioidomycosis Meningococcus, streptococci, Haemophilus Candidiasis influenzae, tuberculosis, leprosy Paracoccidiomycosis Viruses Blastomycosis Arboviruses, herpes viruses, enteroviruses, Nocardiasis* rabies Parasites Indirect effect of infection Protozoans Toxin-mediated infectious diseases (tetanus, malaria (Plasmodium falciparum) diphtheria, shigellosis) African trypanosomiasis (Trypanosoma Immune-mediated postinfectious gambiense and T. rhodesiense) inflammatory (GBS, acute disseminated toxoplasmosis (Toxoplasma gondii) encephalomyelitis) amoebiasis (Entamoeba histolytica) Trematodes (flukes) Metabolic paragonimiasis Hypoglycaemia schistosomiasis (especially Schistosoma Diabetic ketoacidosis japonicum) Hepatic encephalopathy Cestodes (tapeworms) Uraemia cysticercosis (Taenia solium) Hyponatraemia hydatidosis (Echinococcus granulosus) Hypothyroidism/hyperthyroidism Nematodes (roundworms) Addison’s disease ascariasis (Ascaris lumbricoides) parastrongyliasis (Parastrongylus Tumours/trauma/toxins cantonensis) Alcohol gnathostomiasis Drugs (medical, recreational, traditional) trichinosis (Trichinella spiralis) Pesticides Spirochetes Poisons Neurosyphilis (Treponema pallidum) Lyme disease (Borrelia burgdorferi) Other Leptospirosis (Leptospira species) Hydrocephalus Louse-borne/epidemic relapsing fever (B. Epilepsy recurrentis) Psychiatric disease (hysteria) Tick-borne/endemic relasing fever (B. duttonii) Inflammatory Rickettsiae Nutritional Epidemic/louse-borne typhus (Rickettsia Degenerative prowazekii)

Abbreviations: CNS, central nervous system; GBS, Guillain–Barré syndrome. *Nocardia are actinomycete bacteria which are grouped with fungi because of their morphology and behaviour.

Table 3.1 Causes of neurological disease (VIMTO). GBL3 11/27/03 3:43 PM Page 19

Rapid assessment of patient with coma in the tropics 19

CHRONIC NEUROLOGICAL PRESENTATIONS

Infectious Other

Sleeping sickness (especially Trypanosoma rhodesiense,Tumours T. gambiense) Tuberculous meningitis Chronic subdural haemorrhages HIV encephalopathy Lead, other heavy metal poisoning Toxoplasma gondii and other parasitic space-occupying lesions Dementia Bacterial abscesses Vitamin deﬁciencies Partially treated bacterial meningitis Drugs Neurosyphilis Toxins Cryptococcal meningitis and other fungi Subacute sclerosing panencephalitis

Table 3.2 Causes of chronic neurological presentations in the tropics. CNS SPACE-OCCUPYING LESIONS

Tumours and metastases Pathological processes Haemorrhage These neurological syndromes are explained by Bacterial abscesses a range of pathological processes. Tuberculomas • Encephalitis — inflammation of the brain sub- Parasites stance, usually in response to viral infection, but Protozoa (toxoplasmosis, amoebiasis) Trematodes (paragonimiasis, also in response to other pathogens. schistosomiasis) • Meningitis — inflammation of the meningeal Cestodes (cysticercosis, hydatidosis) membranes covering the brain, in response to Nematodes (ascariasis) bacterial, viral or fungal infection. Fungi • Myelitis — inflammation of the spinal cord.This Aspergillosis, blastomycosis, nocardiasis may occur across the whole cord (causing transverse myelitis, which is often postinfec- Table 3.3 Causes of central nervous system tious) or be confined to the anterior horn cells. space-occupying lesions in the tropics. • Neuropathy — damage to peripheral nerves (e.g. Guillain–Barré syndrome, diphtheria, lep- •Airways. rosy, rabies, vitamin deficiencies). •Breathing — give oxygen; intubate if breath- • Space-occupying lesions (Table 3.3) — these ing is inadequate or gag reflex impaired. cause pathology in the brain or spinal cord di- • Circulation — establish venous access. rectly (by interrupting neuronal pathways), and Obtain blood for immediate bedside blood indirectly (by causing localized swelling, raised glucose test (hypoglycaemia?). intracranial pressure and brainstem herniation Malaria film (look for parasites and pigment syndromes). Typically, they present with focal of partially treated malaria). signs or a chronic insidious deterioration. FBC, U&E, blood cultures, arterial blood gases. • Disability. Rapid assessment of patient Give intravenous (i.v.) glucose (e.g. 10% with coma in the tropics glucose 50·mL in adults, 5·mL/kg in children), irrespective of blood glucose. 1 Stabilize the patient, and treat any imme- Give adults 100·mg thiamine i.v., especially if diately life-threatening conditions. alcohol abuse is suspected. GBL3 11/27/03 3:43 PM Page 20

20 Chapter 3: Neurological Presentations

Immobilize cervical spinal cord if neck trau- • Note temperature (febrile or hypother- ma is suspected. mia) and blood pressure (hypo- or hyperten- •Rapidly assess AVPU scale (alert, responds sive). to voice, to pain, or unresponsive). • Examine for signs of trauma (check ears If patient responds to pain or is unresponsive, and nose for blood or cerebrospinal fluid examine the pupils, eye movements, respira- (CSF) leak). tory pattern, tone and posture for signs of • Smell the breath for alcohol or ketones cerebral herniation (see below). (diabetes?). If herniation is suspected start treatment for • Examine the skin for: this. rash (meningococcal rash, dengue or other • If purpuric rash is present give penicillin haemorrhagic fever, typhus, relapsing or chloramphenicol (or third generation fever); cephalosporin) for presumed meningococcal needle marks of drug abuse; meningitis (after taking blood cultures). recent tick bite or eschar (tick-borne en- • Look for and treat generalized seizures, cephalitis, tick paralysis, tick-borne typhus focal seizures and subtle motor seizures or relapsing fever); (mouth or finger twitching, or tonic eye devi- chancre, with or without circinate rash ation). (trypanosomiasis, especially Tr ypanosoma 2Take a history, while preliminary assess- rhodesiense); ment and resuscitation proceeds.This is the sin- healed dog bite (rabies); or gle most useful tool in determining the cause of snake bite. coma. In particular: • Examine for lymphadenopathy (e.g. • Duration of onset of coma. Winterbottom’s sign of posterior cervical Rapid onset (minutes–hours) suggests a lymphadenopathy in African trypanosomiasis). vascular cause, especially brainstem • Examine the fundi for papilloedema (long- cerebrovascular accidents or subarach- standing raised intracranial pressure) or signs noid haemorrhage. If preceded by hemi- of hypertension. spheric signs, then consider intracerebral 4 Determine the coma score to allow sub- haemorrhage. Coma caused by some in- sequent changes to be accurately monitored. fections (e.g. malaria, encephalitis) can also The scale in Box 3.1 is for adults and children over develop rapidly, especially when precipit- 5 years of age and in Box 3.2 for young children. ated by convulsions. 5 Neurological examination. A detailed Intermediate onset (hours–days) suggests description of the neurological examination is diffuse encephalopathy (metabolic or, if beyond the scope of this chapter.For most prac- febrile, infectious). tical purposes the ability to recognize the fol- Prolonged onset (days–weeks) suggests lowing four clinical patterns (and combinations tumours, abscess or chronic subdural of them) will allow appropriate classification haematoma (see Table 3.2). and subsequent investigation and treatment. •Any drugs? • Meningism — with or without enceph- •Any trauma? alopathy. •Important past medical history (e.g. • Diffuse encephalopathies — usually metabol- hypertension)? ic or infectious. • Family history (e.g. tuberculosis)? • Supratentorial focal damage (above the • Known epidemic area (e.g. viral cerebellar tentorium) — usually manifests as encephalitis)? hemispheric signs. 3Perform a rapid general medical exam- • Damage in the diencephalon or brainstem ination, and in particular: (midbrain, pons or medulla) — may indicate a • Check pockets for drugs. syndrome of cerebral herniation through the GBL3 11/27/03 3:43 PM Page 21

Rapid assessment of patient with coma in the tropics 21

MIDLINE HERNIATION SYNDROMES

Key abnormal findings Uncal Unilateral dilated pupil, with Uncus ptosis Reduced response on testing OCR/OVR Hemiparesis (ipsilateral)

Diencephalic Small or midsized pupils reactive to light Full deviation on testing OVR Cheyne–Stokes respiration Flexor response to pain and/or decorticate posturing Hypertonia and/or hypereflexia with extensor plantars

Diencephalon intact survival possible intact survival Midbrain/Upper pontine anstentorial herniation— Midsized pupils, fixed to light Tr Reduced response on testing OCR/OVR Hyperventilation Extensor response to pain and/or decerebrate posturing

Midbrain Lower pontine Midsized pupils, fixed to light No response on testing OCR/OVR Pons Shallow or ataxic respiration No response to pain, or leg

Brainstem flexion only Flaccid tone with extensor Medulla plantars

Medullary Pupils dilated and fixed to light No response on testing OCR/OVR

Slow irregular, gasping or herniation— amen magnum intact survival not possible intact survival absent respiration r No response to pain Fo Flaccid tone with no reflexes

Fig. 3.1 Sagittal section of brain showing temporal lobe — this compresses the ipsilateral anatomy and key abnormal ﬁndings of midline third nerve (to cause a palsy of CNIII), and the herniation syndromes, and (above) coronal contralateral cerebral peduncle (to cause an section showing herniation of the uncus of the ipsilateral hemiparesis).

tentorial hiatus or the foramen magnum (Fig. of reversible damage, is usually more 3.1). The importance of these syndromes important than determining their exact is being increasingly recognized in non- localization. traumatic coma (particularly that caused by Assessment of the following five points al- infections). Although the level of brainstem lows most patients to be classified. damage is given in brackets below (and in Fig. 1 Check for neck stiffness (if no trauma), 3.1), recognizing the presence or absence of and Kernig’s sign (extension of knee when hip is brainstem signs, and in particular early signs already flexed causes pain). GBL3 11/27/03 3:43 PM Page 22

22 Chapter 3: Neurological Presentations

COMA SCALE FOR ADULTS BLANTYRE COMA SCALE AND CHILDREN OVER 5 FOR YOUNG CHILDREN YEARS Best motor response Best motor response 2 Localizes painful stimulus 6 Obeys command 1Withdraws limb from pain 5 Localizes supraorbital pain 0 Non-speciﬁc or absent response 4Withdraws from pain on nail bed Best verbal response 3 Abnormal ﬂexion response 2 Appropriate cry 2 Abnormal extension response 1 Moan or inappropriate cry 1 None 0 None

Best verbal response Eye movements 5 Oriented 1 Directed (e.g. follows mother’s face) 4 Confused 0 Not directed 3 Inappropriate words 2 Incomprehensible sounds Box 3.2 Blantyre coma scale for young children. 1 None Total score is sum of best score in each of three categories (maximum score 5).‘Unrousable coma’ Eye opening reflects score <2 4 Spontaneous 3To voice 2Pain response indicates that the brainstem is in- 1 None tact (diffuse encephalopathy). Reduced or absent responses occur in uncal herniation, Box 3.1 Modified Glasgow coma scale for adults brainstem damage or, rarely, deep metabolic and children over 5 years.Total score is the sum coma. of best score in each of the three categories • Oculovestibular reflex — caloric response to (maximum score 15).‘Unrousable coma’ reflects a water should be tested if the result of the score <9 oculocephalic reflex is unclear. Check that 2 Examine pupil reaction to light (Fig. 3.1). the eardrum is not perforated, then irrigate A normal reaction (constriction) is seen in a dif- by injecting 20·mL ice-cold water. Nystagmus fuse encephalopathy. A unilateral large pupil is is the normal response and indicates ‘psy- seen in herniation of the uncus of the temporal chogenic coma’. Both eyes deviate towards lobe.The pupils are reactive (small or mid-sized) the irrigated ear in coma with the brainstem in the diencephalic syndrome. Unreactive pupils intact. A reduced or absent response indi- occur in brainstem lesions (mid-sized in mid- cates an uncal syndrome or a damaged brain- brain or pontine lesions; large in medullary le- stem. sions). Pinpoint pupils occur following opiate or 4 Assess breathing pattern. A normal organophosphate overdose, or in isolated pon- pattern occurs in diffuse encephalopathy. tine lesion. Other drugs can cause large unreac- Cheyne–Stokes breathing and hyperventilation tive pupils. occur in reversible herniation syndromes. Shal- 3 Assess eye movements (holding eyelids low, ataxic or apnoeic respiration occurs in open if necessary). more severe syndromes (Fig. 3.1). Hyperventi- • Spontaneous eye movements — eyes sponta- lation also occurs in acidosis or may be caused neously roving or eyes following indicates the by aspiration pneumonia, which is common in brainstem is intact (a diencephalic syndrome coma. or a diffuse encephalopathy). 5 Assess response to pain by applying • Oculocephalic (doll’s eye) reflex — when ro- painful stimulus to the supraorbital ridge and tating the head, the eyes normally deviate nail bed of each limb. away from the direction of rotation.A normal • Hemiparesis — most often indicates supra- GBL3 11/27/03 3:43 PM Page 23

Classiﬁcation and further investigation of patients with coma 23

tentorial hemispheric focal pathology (other 3 Coma with focal signs (with or without signs include asymmetry of tone and focal meningism). Decide if the signs are ‘hemispheric seizures), but also occurs in uncal herniation. signs’,‘brainstem signs’, or both. • ‘Decorticate posturing’ — flexion of arms • Hemispheric signs only. If febrile, consider with extension of legs, indicating damage in CNS infection (especially encephalitis, bacte- the diencephalon, and ‘decerebrate posturing’ rial meningitis, abscess, etc.). If afebrile, con- (extension of arms and legs caused by mid- sider space-occupying lesion (Table 3.3), brain/upper pontine damage) may both be cerebrovascular accident or trauma. reversible. No response, or leg flexion only, • Brainstem signs only may be caused by either are more severe. focal pathology within the brainstem (e.g. en- Symmetrical posturing (decorticate or de- cephalitis) especially if markedly asymmetri- cerebrate) and hemiparetic focal signs are cal signs, or by herniation of the brainstem also occasionally seen in metabolic en- (through the foramen magnum) secondary cephalopathies (e.g. hypoglycaemia; hepatic, to a diffuse process (e.g. diabetic ketoacido- uraemic or hypoxic coma; sedative drugs), sis, or late bacterial meningitis) causing raised cerebal malaria, and intra- or postictally. intracranial pressure. Other pointers to metabolic disease include • Hemispheric and brainstem signs may be a asterixis, tremor and myoclonus preceding result of either a supratentorial lesion caus- the onset of coma. ing hemispheric signs and sufficient swelling to precipitate brainstem herniation (e.g. cerebral bleed, abscess) or patchy focal Classification and further pathology in the hemispheres and brainstem investigation of patients (e.g. toxoplasmosis, viral encephalitis). with coma

At this stage, if the history, general examination LUMBAR PUNCTURE and preliminary investigation have not made GUIDELINES one diagnosis extremely likely, most comatose patients will fall into one of three categ- All patients with suspected CNS infection ories, based on the presence or absence of should have a lumbar puncture, except those with the following contraindications: meningism, supratentorial and brainstem signs. • Obtunded state with poor peripheral 1 Coma only (no hemispheric signs, brain- perfusion or hypotension stem signs or meningism — ‘sleeping beauties’). • Deteriorating level of consciousness, or • If patient is febrile (or has a history of deep coma (responsive only to pain, GCS <·8) fever), suspect CNS infection (especially •Focal neurological signs present: cerebral malaria) or metabolic coma plus Unequal, dilated or poorly responsive pupils secondary aspiration pneumonia. Hemiparesis/monoparesis (in patients with coma) • If afebrile, coma is likely to be metabolic Decerebrate or decorticate posturing (hypoglycaemia, drugs, alcohol, diabetic ke- Absent ‘doll’s eye’ movements toacidosis, toxins), psychogenic (test caloric Papilloedema response to water — causes nystagmus), or, • Hypertension and relative bradycardia occasionally, resulting from subarachnoid •Within 30·min of a short convulsive seizure haemorrhage or other cerebrovascular •Following a prolonged convulsive seizure or tonic seizure accident.

2 Coma with meningism, but no focal signs. Abbreviation: GCS, Glasgow coma score. • If febrile, CNS infection (especially bact-

erial meningitis) is likely. Table 3.4 Guidelines for lumbar puncture in • If afebrile, subarachnoid haemorrhage is patients with suspected central nervous system likely. (CNS) infections. GBL3 11/27/03 3:43 PM Page 24

24 Chapter 3: Neurological Presentations

CSF FINDINGS

Acute bacterial Viral meningo- Tuberculous meningitis encephalitis meningitis Fungal Normal

Opening Increased Normal/increased Increased Increased 10–20·cm* pressure

Colour Cloudy ‘Gin’ clear Cloudy/yellow Clear/cloudy Clear

Cells/mm3 High–very high Normal–high Slightly Normal–high increased 1000–50·000 0–1000 25–500 0–1000 <5

Differential Neutrophils Lymphocytes Lymphocytes Lymphocytes Lymphocytes

CSF·:·plasma Low Normal Low–very low Normal–low 66% glucose ratio (e.g. <30%)

Protein (g/L) High Normal–high High–very high Normal–high >1 0.5–1 1–5 0.2–5.0 <·0.5

Normal values Normal CSF opening pressure is <·20·cm water for adults, <·10·cm for children below age 8. A normal CSF glucose is usually quoted to be 66% that of the plasma glucose, but in many tropical settings a cut-off of 40% is found to be more useful. A bloody tap will falsely elevate the CSF white cell count and protein.To correct for a bloody tap, subtract 1 white cell for every 700 red blood cells/mm3 in the CSF,and 0.1·g/dL of protein for every 1000 red blood cells. Some important exceptions In patients with acute bacterial meningitis that has been partially pretreated with antibiotics (or patients <·1 year old) the CSF cell count may not be very high and may be mostly lymphocytes. In viral CNS infections, an early lumbar puncture may give predominantly neutrophils, or there may be no cells in early or late lumbar punctures. Tuberculous meningitis may have predominant CSF polymorphs early on. Listeriosis can give a similar CSF picture to tuberculous meningitis, but the history is shorter. CSF ﬁndings in bacterial abscesses range from near normal to purulent, depending on location of the abscess and whether there is associated meningitis or rupture. An Indian ink test, and if negative a cryptococcal antigen test, should be performed on the CSF of all patients in whom cryptococcosis is possible.

Table 3.5 Cerebrospinal fluid (CSF) findings in dustrialized nations. It has gone out of fashion in central nervous system infections. the latter, following concerns that it was being performed on patients with contraindications, and may have precipitated herniation. In patients with a contraindication, treatment Indications and should be started and then a lumbar puncture contraindications for lumbar reconsidered later. In many tropical settings in puncture in suspected CNS Africa and Asia, where CNS infections are very infections (Table 3.4) common, lumbar puncture is still considered an essential investigation. Here the benefits of ac- For many years lumbar puncture was per- curate diagnosis and appropriate treatment may formed in all patients with suspected CNS outweigh the theoretical risk of herniation, and infections, in both the tropics and western in- even patients with relative contraindications GBL3 11/27/03 3:43 PM Page 25