This page intentionally left blank 437 Chapter 27 Neurological disorders Coma 438 Acute weakness 440 Delirium 442 Generalized seizures 444 Meningitis 446 Intracrani al hemorrhage 448 Subarachnoid hemorrhage 450 Stroke 452 Raised intracranial pressure 454 G uillain \200\223Barr syndrome 456 Myasthenia gravis 458 Critical care neuromuscular disor ders 460 Tetanus 462 Botulism 464 438 CHAPTER 27 Neurological disorders Coma Causes \200 Brain injury \200\224e.g. trauma, cerebrovascular accident, meningo- encephalitis, malaria, ictal (or post-ictal), space-occupying lesion. Metabolic \200\224hypoglycaemia or hypergly caemia, severe electrolyte disturbance (e.g. Na+), renal failure, liver failure. Sepsis. Dr ug-related or poisoning \200\224e.g. opiates, benzodiazepines, carbon monoxide poisoning, r ecreational drugs, alcohol. Haemodynamic \200\224related to poor cerebral perfusion (cardia c arrest, severe heart failure, arrhythmia, hypotension). Respiratory \200\224low PaO2 and/ or high PaCO2. Endocrine \200\224e.g. myxoedema, Addison \200\231s disease. Temperature dis turbance (hyperpyrexia, hypothermia). \200 \200 \200 Investigation \200 \200 \200 \200 \200 \200 \200 This is dictated by presenting history and examination \201 ndings. Urgent blood sugar te sting (at the bedside). Urea and electrolytes, sugar (lab-measured), calcium, liver functio n. FBC and clotting screen to exclude coagulopathy. Urgent blood gas analysis (including CO Hb if indicated). Blood and urine poison/drug screen/alcohol level. Plasma creatine kinase and test urine for \200\230positivity \200\231 for blood if rhabdomyolysis possible (immob ility, recreational drugs, hyperpyrexia). Metabolic screen (thyroid function, cortisol). Se ptic screen 9 malaria screen. Lumbar puncture (9 preceding CT scan if concerned about raise d ICP). CT scan. Other neurological tests, e.g. EEG. MRI. \200 \200 \200 \200 Management \200 \200 ABC \200\224ensure adequate (protected) airway, breathing, circulation. Correct rapidly rem ediable causes promptly, e.g. hypoglycaemia, status epilepticus, speci \201 c antidote (e. g. naloxone for opiate toxicity). If meningitis suspected, give antibiotics immediately (e. g. ceftriaxone). Prioritize investigations based on likely diagnosis; treat accordingly. In stitute measures to lower intracranial pressure if concerned about coning. Urgent referral to neurosurgeon if CT demonstrates space-occupying lesion (e.g. haematoma) or for brain dec ompression (craniectomy). Urgent consideration of thrombolysis if cerebral infarct or embol us. Consider duration of coma when treating metabolic abnormality. Correction of Na+ and gl ucose may need to be more gradual. Unconscious patients involved in a traumatic event have an unstable spine until speci \201 cally excluded, and should be managed accordingly. Cons ider active warming (for hypothermia) or cooling (for prolonged cardiac arrest or, possibly , head injury). If rhabdomyolysis present, ensure adequate circulating volume, urinary alka linisation, and relief of any compartment syndrome. DVT prophylaxis. Nursing measures to pr event contractures and pressure sores. \200 \200 \200 \200 COMA 439 See also: Airway maintenance, p40; Endotracheal intubation, p42; Ventilatory support \200 \224indications, p44; Blood gas analysis, p154; Intracranial pressure monitoring, p200; EEG /CFM monitoring, p204; Urea and creatinine, p210; Electrolytes (Na+, K+, Cl \200\223, HCO3 \200\223), p212; Liver function tests, p218; Coagulation monitoring, p222; Toxicology, p22 8; Basic resuscitation, p338; Acute liver failure, p430; Delirium, p442; Generalized seizur es, p444; Meningitis, p446; Intracranial hemorrhage, p448; Subarachnoid hemorrhage, p450; S troke, p452; Raised intracranial pressure, p454; Hypernatraemia, p484; Hyponatraemia, p486; Hypocalcaemia, p496; Hypoglycaemia, p506; Hyperglycaemia, p508; Diabetic ketoacidosis, p51 0; Hyperosmolar diabetic emergencies, p512; Poisoning \200\224general principles, p520; Sed ative poisoning, p526; Infection \200\224diagnosis, p552; Head injury (1), p586; Head injur y (2), p588; Brain stem death, p652. 440 CHAPTER 27 Neurological disorders Acute weakness Severe acute weakness may require urgent intubation and mechanical ven- tila tion if the FVC <1L or gas exchange deteriorates acutely. Critical illness neuromyopathy pr esents with generalized weakness 9 loss of sensation. It becomes apparent on reducing sedat ion in critically ill patients and is likely to be a neuromuscular manifestation of multipl e organ failure. Causes \200 \200 Critical illness neuromyopathy. New onset CVA \200\224usually unilateral \200\224increased risk in critical care patients with cerebral hypoperfusion and/or coagulopathy. Metabolic m yopathies \200\224treat low K+, Mg2+, Ca2+, phosphate. Prolonged effects of muscle relaxant s \200\224consider low pseudocholinesterase levels or myasthenia if occurs after suxamethon ium use. Prolonged effects of non-depolarising muscle relaxants are suggested by response t o an anticholinesterase (neostigmine 2.5mg slow IV bolus with an anticholinergic). Patients with myasthenia gravis also respond. Cord compression. Guillain \200\223Barr syndrome \200\224lumbar puncture will con \201 rm raised CSF protein with normal cells. If not foun d but suspicion remains strong, nerve conduction studies may demonstrate segmental demyelin ation with slow conduction velocities. Myasthenia gravis \200\224fatigable weakness or ptos is suggests myasthenia gravis; response to IV edrophonium (Tensilon test) and a strongly positive acetylcholine receptor antibody titre are con \201 rmatory. Myasthenic syndrome a ssociated with malignancy (Eaton \200\223Lambert syndrome) often involves pelvic and thigh muscles, and tends to spare ocular muscles. Other diagnoses are made largely on the basis o f clinical suspicion and specialized tests. \200 \200 Management \200 Correction of electrolyte and metabolic abnormalities and removal (if possible) of potentia lly contributory factors, e.g. corticosteroids. For Guillain \200\223Barr , monitor FVC 2 \200\2234 hourly; intubate and mechanically ventilate if FVC <1L. Give IV Ig and consider p lasmapheresis. Other indices of respiratory function are less sensitive. In particular, art erial blood gasses may be maintained up to the point of respiratory arrest. Weak respirator y muscles lead to progressive basal atelectasis and sputum retention. Chest infection is a signi \201 cant risk; regular chest physiotherapy with intermittent positive pressure brea thing is required for prevention where mechanical ventilation is not necessary. Give DVT pr ophylaxis to immobile patients. They also require attention to posture to prevent pressure sores and contractures. Weak bulbar muscles may compromise swallowing with consequent malnu trition or pulmonary aspiration. Enteral nutritional support via a nasogastric tube is nece ssary. In cases with coexistent autonomic neuropathy, enteral nutrition may be impossible, necessitating parenteral nutritional support. They may also suffer arrhythmias and hypotens ion requiring appropriate support. ACUTE WEAKNESS 441 Causes of severe generalized weakness Common in ICU Uncommon in ICU Metabolic myopathies Endocrine myopathy Prolonged effects of muscle relaxants Lead poisoning Critical illness neuromyopathy Organophosphorus poisoning Guillain \200\223Barr syndrome Botulism Myasthenia gravis Chronic relapsing polyneuritis Pontine CVA Sarcoid neuropathy Substance abuse (especially benzene ring compounds) Poliomyelitis Multiple sclerosis Diphtheria Familial periodic paralysis Porphyria See also: Airway maintenance, p40; Endotracheal intubation, p42; Ventilatory support \200 \224indications, p44; IPPV \200\224assessment of weaning, p60; Pulmonary function tests, p1 48; Guillain \200\223Barr syndrome, p456; Myasthenia gravis, p458; Critical care neuromus cular disorders, p460; Tetanus, p462; Botulism, p466. 442 CHAPTER 27 Neurological disorders Delirium In the ICU, agitation and/or confusion are predominantly related to loss of day-ni ght rhythm and inability to sleep, sepsis, cerebral hypoperfusion, or drugs (or their withd rawal). Delirium is related to increased mortality. \200\230ICU psychosis \200\231 is a co mmon occurrence in the patient recovering from severe illness. \200\230Silent delirium \200\231, usually presenting as a withdrawn, non- communicative patient, is signi \201 can tly under-recognized. Common ICU causes \200 Infection: including generalized sepsis, chest, cannula sites, urinary tract. Cerebral infe ction such as meningitis, encephalitis and malaria are relatively rare but should always be considered. Drug-related: (i) adverse reaction (particularly in the elderly), e.g. to seda tives, analgesics, diuretics, (ii) withdrawal, e.g. sedatives, analgesics, ethanol, (iii) a buse, e.g. opiates, amphetamines, alcohol, hallucinogens. Metabolic: e.g. hypoglycaemia or hyperglycaemia, hyponatraemia or hypernatraemia, hypercalcaemia, uraemia, hepatic encephalo pathy, hypothermia or hyperthermia, dehydration. Respiratory: infection, hypoxaemia, hyperc apnia. Neurological: infection (meningo-encephalitis, malaria), post-head injury/seizure/ca rdiac arrest, space-occupying lesion (e.g. haematoma). Haemodynamic: low output state, hypo tension, endocarditis. Pain: full bladder (blocked Foley catheter), abdominal pain. Psychos is: \200\230ICU psychosis \200\231, other psychiatric states. \200 \200 \200 Principles of management 1. Examine and investigate for signs of: (i) infection, (ii) cardi ovascular in- stability, (iii) covert pain, e.g. full bladder, (iv) focal neurology, e.g. m en- ingism, unequal pupils, hemiparesis, respiratory failure (arterial blood gasses), (v) m etabolic derangement (biochemical screen). 2. If any of the above are found, treat as appropriate. Psychosis should not be assumed until treatable causes are excluded. 3. Reassure and calm the patient. Maintain quiet atmosphere and reduce noise levels. Attemp t to restore day-night rhythm, e.g. by changing am- bient lighting and use of oral hypnotic agents, e.g. temazepam, a tot of alcohol, chloral. 4. Consider starting, changing, or increasing dose of sedative or major tranquilizer to con trol patient. If highly agitated and likely to endan- ger themselves, rapid short-term cont rol can be achieved by a slow IV bolus of sedative. Consider propofol, a benzodiazepine, ha loperidol, or chlorpromazine in the smallest possible dose to achieve the desired effect; o bserve for hypotension, respiratory depression, arrhythmias, and extrapyramidal effects. Op iates may be needed, especially if pain or withdrawal is a factor. An ethanol infusion can be considered for delirium tremens resulting from alcohol withdrawal, but this generally ca nnot be managed on a general ward on ICU discharge. 5. Sedation can be maintained by continuous infusion or intermittent in- jection, either re gularly or as required. The less agitated patient may respond to IM injections of a major t ranquilizer, though these should be avoided with concurrent coagulopathy. 6. There is no strong evidence for the use of antidepressants in ICU. DELIRIUM 443 Drug dosages for severe agitation Haloperidol 2.5mg by slow IV bolus. Repeat, doubling dose, every 10 \200\22315min until effect. For reg ular prescription, give qds. Chlorpromazine 12.5mg by slow IV bolus. Repeat, doubling dose, every 10 \200\22315min until effect. May ne ed up to 100mg. For regular prescription, give qds. Midazolam/diazepam 2 \200\2235mg by slow IV bolus Propofol 30 \200\223100 mg by slow IV bolus Morphine 2.5 \200\2235mg by slow IV bolus NB. Beware excessive central and respiratory depression with opiates, benzodiazepines, and propofol. Confusion assessment method for the ICU CAM-ICU is a validated delirium monitoring instrume nt for use in ICU patients. For more details, see <www.icudelirium.org>. Feature 1: Acute onset or \202 uctuating course Different to baseline mental status or an y \202 uctuation in mental status in the past 24h as evidenced by \202 uctuation on a s edation scale (e.g. RASS), GCS, or previous delirium assessment? Feature 2: Inattention Positive if cannot provide correct answers to number or picture test . Feature 3: Disorganized thinking Positive if fails to answer correctly logical statements ( e.g. can you use a hammer to cut wood?) or to perform simple repetitive commands. Feature 4: Altered level of consciousness Positive if RASS or other sedation score is anyth ing other than normal. Overall CAM-ICU score: Presence of features 1 and 2 and either feature 3 or 4 is positive f or delirium. Key papers Ely EW, Inouye SK, Bernard GR et al. (2001) Delirium in mechanically ventilated patients: validity and reliability of the confusion assessment method for the intensive car e unit (CAM-ICU). JAMA 286: 2703 \200\22310. Sessler CN, Gosnell M, Grap MJ et al. (2002) The Richmond Agitation-Sedation Scale: validit y and reliability in adult intensive care patients. Am J Respir Crit Care Med 166: 1338 \200\22344. Girard TD, Kress JP, Fuchs BD, et al. (2008) Ef \201 cacy and safety of a paired sedation and ventilator weaning protocol for mechanically ventilated patients in intensive care (Awa kening and Breathing Controlled trial): a randomized controlled trial. Lancet 371: 126 \200 \22334. See also: IPPV \200\224failure to tolerate ventilation, p52; Toxicology, p228; Sedatives an d tranquilisers, p308; Coma, p438; Generalized seizures, p444; Meningitis, p446; Infection \200\224diagnosis, p552; Malaria, p568; Head injury (1), p586; Head injury (2), p588; Pain, p618; Pain and comfort, p624. 444 CHAPTER 27 Neurological disorders Generalized seizures Control of seizures is necessary to prevent ischaemic brain damage, re duce cerebral oxygen requirements, and reduce intracranial pressure. Where possible, correc t the cause and give speci \201 c treatment. A CT scan may be necessary to identify struct ural causes. Common causes include: \200 \200 \200 \200 \200 \200 \200 \200 \200 Most seizures are self-limiting, simply needing protection from injury (coma positi on, protect head). Do not force anything into the mouth. Hypoxaemia. Hypoglycaemia. Abnormal plasma Ca2+, Na+, and Mg2+ levels. Space-occupying lesi ons. Metabolic and toxic disorders, e.g. liver failure, renal failure. Drug withdrawal, e.g . alcohol, benzodiazepines, anticonvulsants. Infection, especially meningo-encephalitis. Tr auma. Idiopathic epilepsy. Speci \201 c treatment \200 \200 Correct hypoxaemia with oxygen (FIO2 0.6 \200\2231.0). Intubate and ventilate if the airway is unprotected or the patient remains hypoxaemic despite breathing a high FIO2. Urgently m easure blood glucose and treat hypoglycaemia with 50% glucose 25 \200\22350mL IV. Correct a nticonvulsant levels in known epileptics. Manage cerebral oedema with sedation, induced hyp othermia, controlled hyperventilation, and osmotic diuretics. In patients with a known tumo r, arteritis, or parasitic infection, high- dose dexamethasone may be given. Give thiamine 100mg IV to alcoholics and malnourished individuals. Consider surgery for space-occupying l esions, e.g. blood clot, tumor. \200 \200 Anticonvulsants Anticonvulsants are necessary where there are repeated seizures, a single s eizure lasts >30min, or there is cyanosis. \200 \200 Benzodiazepines (e.g. lorazepam, diazepam) are \201 rst-line treatment. Phenytoin: give a loading dose IV if patient has not previously received phenytoin. Phenytoin may not provid e immediate control of seizures within the \201 rst 24h. If seizures continue, other appropriate anticonvulsants include: \200 \200 \200 \200 With all anticonvulsants, care should be taken to avoid hypoventilation and respiratory f ailure. Mechanical ventilation will be required to maintain oxygenation in cases of continu ed seizures. Magnesium sulfate. Clonazepam, which is particularly useful for myoclonic seizures. Propofo l infusion. Thiopental infusion in severe intractable epilepsy. Other supportive treatment Muscle relaxants prevent muscular contraction during seizures, b ut will not prevent continued seizures. They may be necessary to facilitate mechanical vent ilation, but continuous (or repeated) EEG monitoring should be used to judge seizure contro l. Maintain optimal circulation and cerebral blood \202 ow. generalized SEIZURES 445 Drug dosages Lorazepam 4mg IV Diazepam Initially 2.5 \200\2235mg IV or PR. Further increments as necessary to a maximum of 20mg. Midazolam Initially 2.5 \200\2235mg IV or PR. Further increments as necessary to a maximum of 20mg. Phenytoin Loading dose 18mg/kg IV at a rate <50mg/min with continuous ECG monitoring. Maintenance at 300 \200\223 400mg/d IV, IM, or PO, adjusted according to levels. Magnesium sulfate Initially 20mmol over 3 \200\2235min, followed by 5 \200\22310mmol/h by infusion as necessa ry. Clonazepam 1mg/h IV Thiopental 1 \200\2233mg/kg IV, followed by lowest dose to maintain control Propofol 0.5 \200\2232mg/kg IV, followed by 1 \200\2233mg/kg/h Key paper Treiman VA for the Veterans Affairs Status Epilepticus Cooperative Study Group. ( 1998) A com- parison of four treatments for generalized convulsive status epilepticus. N En gl J Med 339: 792 \200\2238. See also: Airway maintenance, p40; Endotracheal intubation, p42; Ventilatory support \200 \224indications, p44; \210\222 \210\222 EEG/CFM monitoring, p204; Electrolytes (Na+, K+, Cl ), p212; Calcium, magnesium, and , HCO3 phosphate, p214; Anticonvulsants, p310; Respirat ory failure, p350; Acute renal failure \200\224diagnosis, p400; Acute liver failure, p430; Hepatic encephalopathy, p432; Chronic liver failure, p434; Meningitis, p446; Intracranial h emorrhage, p448; Stroke, p452; Raised intracranial pressure, p454; Hyponatraemia, p486; Hyp omagnesaemia, p492; Hypocalcaemia, p496; Hypoglycaemia, p506; Head injury (1), p586; Head i njury (2), p588. 446 CHAPTER 27 Neurological disorders Meningitis A life-threatening condition demanding prompt treatment. As classical features o f meningism may be absent, suspect in those presenting with obtundation, agitation, seizure s, or focal neurology. Signs may be subtle or present insidiously in neutropaenics and the elderly. Meningococcaemia presents with a prominent rash in only 30% of cases, while Lister ia (L.) monocytogenes may cause early seizures and focal neurology. Diagnosis \200 Bacterial meningitis is primarily diagnosed by CSF examination. Send lumbar puncture (LP) s amples for urgent microscopy and culture, PCR, virology, protein and glucose estimation (+ concurrent plasma sample). Normal or lymphocytic CSF may be found in early pyogenic meningi tis, especially L. monocytogenes. Raised ICP is common; LP (but not antibiotics) should be delayed until after the CT scan. A normal CT scan does not exclude raised ICP). Start empir ical antibiotic therapy with concurrent corticosteroids immediately after taking blood cult ures. CSF cultures are positive in 50% if antibiotics are given and 60 \200\22390% in untre ated cases. CSF bacterial antigen testing is available for most infecting organisms; sensit ivity varies from 50 \200\223100% while speci \201 city is high. Management 1. Antibiotic therapy, usually for \211 10 days though recent studies suggest equal ef \201 cacy with shorter courses. 2. Dexamethasone 10mg qds for four days should be started with or just before the \201 rs t dose of antibiotic. Outcome bene \201 t has been shown for pneumococcal meningitis thoug h it is recommended for all. 3. General measures include attention to \202 uid and electrolyte replace- ment, adequate gas exchange, nutrition, and skin care. 4. Management of raised intracranial pressure if present. 5. Oral cipro \202 oxacin (adults only) or rifampicin should be give n to family and close social contacts of meningococcal and haemophilus meningitis. The inde x case should also be treated before discharge. Aseptic meningitis No organisms are identi \201 ed by routine CSF analysis despite a high neu- trophil and/or lymphocyte count. Causes include viruses (e.g. mumps, measles), fungi, leptospirosis, listeriosis, brucellosis, atypical TB, SLE. Encephalitis Presenting features include drowsiness, coma, agitation, pyrexia, seizures, an d focal signs; meningism need not necessarily be present. Causes \200 \200 Bacterial (as for meningitis). Viruses (in particular, herpes simplex and up to 14 days exa nthemata). Herpes simplex classically affects the temporal lobe and can be diagnosed by EEG . Aciclovir 10mg/kg tds IV is given for ten days. Rarer causes include leptospirosis and br ucellosis; CSF reveals no organisms but a high lymphocyte count. If indicated, send CSF for acid fast stain (TB) and India Ink stain (Cryptococcus). MENINGITIS 447 Typical CSF values in meningitis Pyogenic Viral Tuberculosis Classical appearance Turbid Clear Fibrin web Predominant cell type Cell count/mm3 Polymorphs Lymphocytes Lymphocytes >1000 <500 50 \200\2231500 Protein (g/L) >1 0.5 \200\2231 1 \200\2235 CSF:blood glucose <60% >60% <60% Organisms and empirical starting antibiotic therapy Organism Patients often affected Antibiotic and dosage regimen (alternatives in brackets) Neisseria meningitidis Young adults Ceftriaxone 2 \200\2234g IV od (cefotaxime 50mg/kg IV 8-hourly) (benzylpenicillin 1.2g IV 2 \200\2234 hourly) (chloramphenicol 12.5mg/kg IV 6-hourly) (Meningococcus) Older adults Ceftriaxone 2 \200\2234g IV od (cefotaxime 50mg/kg IV 8-hourly) (chloramphenicol 12.5mg/kg IV 6-hourly) Streptococcus pneumoniae (Pneumococcus) Haemophilus in \202 uenzae Children Ceftriaxone 20 \200\22350mg/kg IV od (cefotaxime 50mg/kg IV 8-hourly) (chloramphenicol 12.5 mg/kg IV 6-hourly) Ampicillin 1g IV 4 \200\2236 hourly plus gentamicin 120mg IV stat, then 80mg 8 \200\22312 h ourly (adjust by plasma levels) Elderly, immuno- compromised Listeria monocytogenes Rifampicin/isoniazid/ethambutol/ pyrazinamide Mycobacterium tuberculosis Cryptococcus neoformans Immuno- compromised Amphotericin B starting at 250mcg/kg IV od + \202 ucytosine 50mg/kg IV 6-hourly Staphylococcus aureus Flucloxacillin 2g IV 6-hourly(vancomycin, teicoplanin, or linezolid (600mg IV 12hourly), of ten + rifampicin if MRSA) Key papers de Gans J, van de Beek D; European Dexamethasone in Adulthood Bacterial Meningit is Study Investigators. (2002) Dexamethasone in adults with bacterial meningitis. N Engl J Med 347: 1549 \200\22356. van de Beek D, de Gans J, McIntyre P, et al. (2007) Corticosteroids for acute bacterial men ingitis. Cochrane Database Syst Rev 24;(1): CD004405. See also: Bacteriology, p224; Virology, serology, and assays, p226; Antimicrobials, p326; C orticosteroids, p330; Basic resuscitation, p338; Coma, p438; Delirium, p442; Generalized se izures, p444; Raised intracranial pressure, p454; Infection control \200\224general princip les, p544; Infection control \200\224dangerous pathogens, p548; Infection \200\224diagnosis , p552; Infection \200\224treatment, p554. 448 CHAPTER 27 Neurological disorders Intracranial hemorrhage Extradural hemorrhage Usually presents acutely after head injury. C haracterized by falling Glasgow coma score progressing to coma, focal signs (lateralising w eakness or anesthesia, pupillary signs), visual disturbances, and seizures. Treatment by ra ndom burr holes has been supplanted by directed drainage following CT scan localization. A conservative approach may be adopted for small haematomata, but increasing size (assessed by regular CT scanning or clinical deterioration) are indications for surgical drainage. Subdural hemorrhage Classically presents days to weeks following head trauma with a \202 uctuating level of consciousness (35%), agitation, confusion, seizures, and signs of raised intracranial pressure, localizing signs, or a slowly evolving stroke. Diagnosis is made by CT scan. Treatment is by surgical drainage. Intracerebral hemorrhage Causes include hypertension, neoplasm, vasculitis, coagulopathy, a nd mycotic aneurysms associated with bacterial endocarditis. Clinical features include sudden onset coma, drowsiness and/or neu- rological de \201 cit. Headache usually occurs only with cortical and intraven- tricular hemorrhage. The rate of evolution depends on the size and size of the bleed. The area affected is the putamen (55%) , thalamus (10%), cer- ebral cortex (15%), pons (10%), and cerebellum (10%). Diagnosis CT scan is the de \201 nitive test. A coagulation and vasculitis blood screen ma y be indicated. Angiography is indicated if surgical repair is contem- plated though not fo r drainage of blood clot. Treatment \200 Bed rest. \200 Supportive (e.g. hydration, nutrition, analgesia, ventila tory support). \200 Physiotherapy. \200 Blood pressure control (maintain systolic BP <2 20 \200\223230mmHg). \200 Correct any coagulopathy. \200 Control raised intracranial pr essure. \200 Surgery \200\224contact Regional Center, e.g. for evacuation of haematoma, r epair/clipping of aneurysm. Corticosteroid therapy is ineffective. INTRACRANIAL hemorrhage 449 See also: Coagulation monitoring, p222; Hypotensive agents, p270; Neuroprotective agents, p 312; Coma, p438; Subarachnoid hemorrhage, p450; Stroke, p452; Raised intracranial pressure, p454; Bleeding disor- ders, p468; Head injury (1), p586; Head injury (2), p588; Brain stem death, p652. 450 CHAPTER 27 Neurological disorders Subarachnoid hemorrhage Pathology \200 In 15%, no cause is found; of the remainder, 80% are due to a ruptured aneurysm, 5% to arte riovenous malformations, and 15% follow trauma. The anterior part of the Circle of Willis i s affected in 90 \200\22395% of subarachnoid hemorrhage (SAH) while 10 \200\22315% affect t he vertebrobasilar system. There is a 30% risk of rebleeding for which the mortality is 40% . Those surviving a month have a 90% chance of surviving a year. Cerebral vasospasm occurs in 30 \200\22340% of patients at 4 \200\22312 days after the bleed. This is the most import ant cause of morbidity and mortality. Hydrocephalus, seizures, hyponatraemia, and inappropr iate ADH secretion are recognized complications. Clinical features \200 SAH may be preceded by a prodrome of headache, dizziness, and vague neurological symptoms. Often there is rapid onset (minutes to hours) presentation, including collapse, severe head ache 9 meningism. Cranial nerve palsies, drowsiness, and hemiplegia may also occur. Diagnosis Diagnosis is usually made by CT scan; if there is no evidence of raised intracran ial pressure, a lumbar puncture may be performed revealing bloodstained CSF with xanthochro mia. Management \200 Bed rest. \200 Maintain adequate hydration, nutrition, analgesia, sedat ion. \200 Cerebral vasospasm is prevented by nimodipine infusion and maintenance of a ful l intravascular volume. Systemic hypertension should only be treated if severe (e.g. systol ic pressure >220 \200\223230mmHg) and prolonged. Surgery: the timing is controversial with either early or delayed (7 \200\22310 days) intervention being advocated. The Regional Neur osurgical Center should be consulted for local policy. Anti \201 brinolytic therapy (e.g. tranexamic acid) reduces the incidence of rebleeding, but has no bene \201 cial effect on outcome. SUBARACHNOID hemorrhage 451 Key paper Allen GS, Ahn HS, Preziosi T J, et al. (1983) Cerebral arterial spasm \200\224a c ontrolled trial of nimodipine in patients with subarachnoid hemorrhage. N Engl J Med 308: 6 19 \200\22324. See also: Blood pressure monitoring, p164; Hypotensive agents, p270; Neuroprotective agents , p312; Coma, p438; Intracranial hemorrhage, p448; Stroke, p452; Raised intracranial pressu re, p454; Bleeding disorders, p468; Head injury (1), p586; Head injury (2), p588; Brain ste m death, p652. 452 CHAPTER 27 Neurological disorders Stroke Pathology \200 \200 Haemorrhagic, embolic or thrombotic. \200\230Secondary \200\231 stroke may occur with meni ngitis, bacterial endocarditis, subarachnoid hemorrhage, and vasculitis. Dissection and cer ebral venous thrombosis need to be considered, as anticoagulation is indicated for both (un less a large infarct is established as there is an increased risk of bleeding). Dissection should be suspected in younger patients, often presenting with severe headache or neck pain 9 Horner \200\231s syndrome 9 seizures after trauma or neck manipulation. Cerebral venous thrombosis may mimic stroke, tumor, subarachnoid hemorrhage, or meningo-encephalitis, and m ay present with headache, seizures, focal signs, or obtundation. Urgent CT scan Indicated when the diagnosis is in doubt, for continuing deterioration, susp icion of subarachnoid hemorrhage, hydrocephalus or trauma, or for patients who are anticoag ulated or who have a bleeding tendency. Aims of treatment \200 To protect the penumbra with close attention to oxygenation, hydration, tight glycaemic con trol, and avoidance of pyrexia. Blood pressure control is needed for severe hypertension (e .g. >200/120mmHg) and for hypotension. Aspirin is given early for thrombotic stroke. The ev idence for full anticoagulation is contentious as there is an increased risk of bleeding an d no consistent subgroup bene \201 t has been shown. Early anticoagulation probably bene \201 ts intracranial stenosis, stroke-in- evolution, complete vessel occlusion with minimal de \201 cit, and in low-risk patients with a high probability of recurrence (secondary pr evention). For thrombolysis, reperfusion extent depends on etiology with basilar > middle c erebral artery > internal carotid, and embolic > thrombotic. Studies with rtPA (0.9mg/kg) g iven within 3h of stroke onset (and tight BP control) show favorable outcomes. However, the re was a 6-fold increase in hemorrhage (to 5.9%), of whom 60% died. This was more common in the elderly and with more severe stroke. Some centers perform intra-arterial or ultrasound -enhanced thrombolysis. Neurosurgical intervention 9 decompression may be considered for ce rebellar haematoma, cerebellar infarction, and the \200\230malignant middle cerebral arter y syndrome \200\231 (for massive infarction on the non-dominant side). Therapeutic hypother mia is theoretically bene \201 cial but no large trial has yet been performed. Concerns in clude an increased risk of hemorrhage and rebound intracranial hypertension on rewarming. STROKE 453 Key paper Hacke W , Donnan G, Fieschi C, et al. (2004) Association of outcome with early st roke treatment: pooled analysis of ATLANTIS, ECASS, and NINDS rt-PA stroke trials. Lancet 3 63: 768 \200\22374. See also: Oxygen therapy, p38; Ventilatory support \200\224indications, p44; Therapeutic hy pothermia, p100; Tight glycaemic control/intensive insulin therapy, p132; Blood pressure mo nitoring, p164; Neuroprotective agents, p312; Thrombolytics, p316; Basic resuscitation, p33 8; Coma, p438; Generalized seizures, p444; Intracranial hemorrhage, p448; Subarachnoid hemo rrhage, p450; Raised intracranial pressure, p454. 454 CHAPTER 27 Neurological disorders Raised intracranial pressure Clinical features \200 \200 \200 \200 \200 \200 \200 Headache, vomiting, dizziness, visual disturbance. Seizures, focal neurology, papilloedema. Increasing blood pressure, bradycardia (late responses). Agitation, increasing drowsiness, coma. Slow deep breaths, Cheyne \200\223Stokes breathing, apnoea. Ipsilateral progressing to bilateral pupillary dilatation. Decorticate progressing to decerebrate posturing. Diagnosis \200 \200 CT scan or MRI. Intracranial pressure (ICP) measurement >20mmHg. Lumbar puncture should be avoided because of the risk of coning. Neither CT scan nor absenc e of papilloedema will exclude a raised ICP. Management 1. Bed rest, 20 \200\22330* head-up tilt, sedation, quiet environment, minimal s uction and noise. Sedation and B-blockade are often necessary to overcome a hyperadrenergic state, but sedative-induced hypotension should be avoided. The tape tethering the endotrac heal tube in place should not occlude jugular venous drainage. 2. Ventilate if GCS \211 8, airway unprotected, or excessively agitated. 3. Maintain PaCO2 at 4 \200\2234.5kPa and avoid rapid rises. CSF bicarbonate levels re-equilibrate within 4 \200\2236h, negating any bene \201 t from hyperventilation. 4. If available and not contra indicated, monitor ICP. Aim to maintain ICP <20mmHg and cerebral perfusion pressure (= MAP \200\223 ICP) >70mmHg. Vasopressor therapy may be needed. Do not treat systemic hyperten- sion unless very high (e.g. systolic >220 \200\223230mmHg). 5. Other monitoring techniques, e.g. jugular bulb venous saturation (SjO2) and lactate, may be useful though they do not detect regional ischaemia. 6. Give mannitol 0.5mg/kg IV over 15min. Repeat at 4-hourly intervals depend- ing on cerebral perfusion pressure (CPP) measur ements and/or clinical signs of deterioration. Stop when plasma osmolality reaches 310 \200 \223320mOsm/kg. 7. Avoid severe alkalosis as cerebral vascular resistance rises and cerebra l ischaemia increases. 8. Consider speci \201 c treatment, e.g. for meningo-encephalitis, malaria, he- patic ence phalopathy, surgery. Some neurosurgeons will decompress the cranium for generalized oedema by removing a skull \202 ap. Seek local advice. Dexamethasone 4 \200\22316mg qds IV is be ne \201 cial for oedema sur- rounding a tumor or abscess and for herpes simplex encephalit is. Acute deterioration/risk of imminent coning 1. Mechanically ventilate to PaCO2 3.0 \200\223 3.5kPa for 10 \200\22320min. 2. Give mannitol 0.5g/kg IV over 15min. Repeat 4-hourly as nec essary and stop when plasma osmolality >310 \200\223320mOsm/kg. Consider therapeu- tic hypo thermia. 3. If no response in ICP, CPP and/or clinical features, give thiopental (successful in 50% of resistant cases). 4. Consider repeat CT scan and refer for urgent surgery if a surgically- amenable space-occupying lesion is diagnosed. RAISED INTRACRANIAL PRESSURE 455 Causes of raised intracranial pressure \200 \200 Space-occupying lesion (e.g. neoplasm, blood clot, abscess). Increased capillary permeabili ty (e.g. trauma, infection, hepatic encephalopathy). Cell death (e.g. hypoxia). Obstruction (e.g. hydrocephalus). \200 See also: Oxygen therapy, p38; Ventilatory support \200\224indications, p44; Therapeutic hy pothermia, p100; Blood pressure monitoring, p164; Intracranial pressure monitoring, p200; J ugular venous bulb saturation, p202; Other neurological monitoring, p206; Neuroprotective a gents, p312; Basic resuscitation, p338; Acute liver failure, p430; Hepatic encephalopathy, p432; Coma, p438; Generalized seizures, p444; Meningitis, p446; Intracranial hemorrhage, p4 48; Subarachnoid hemorrhage, p450; Stroke, p452; Head injury (1), p586; Head injury (2), p5 88; Brain stem death, p652. 456 CHAPTER 27 Neurological disorders Guillain \200\223Barr syndrome \200 \200 \200 An immunologically mediated acute demyelinating polyradiculopathy. Viral infections and imm unisations are common antecedents. It includes a progressive, are \202 exic motor weakness (often symmetrical, ascending, and involving cranial nerves, including facial, bulbar, and extraocular weakness) with progression over a few days to weeks. There are often minor sen sory disturbances (e.g. paraesthesiae). Autonomic dysfunction is not unusual. There is no i ncrease in cell count on CSF examination, but protein levels usually rise progressively (>0 .4g/L). Nerve conduction studies show slow conduction velocities with prolonged F waves. Ot her features include muscle tenderness and back pain. The major contributors to morbidity a nd mortality are respiratory muscle weakness and autonomic dysfunction (hypotension, hypert ension, arrhythmias, ileus, and urinary retention). \200 \200 \200 Differential diagnosis Other causes of acute weakness must be excluded before a diagnosis o f Guillain \200\223Barr syndrome can be made. Speci \201 c treatment \200 Intravenous immunoglobulin (0.4g/kg/d for \201 ve days) or plasma exchange ( \201 ve 50m L/kg exchanges over 8 \200\22313 days) is effective if started within 14 days of onset of s ymptoms. Corticosteroids have not been shown to be bene \201 cial. Supportive treatment Respiratory care Regular chest physiotherapy and spirometry are requir ed. Mechanical ven- tilation is needed if FVC <1L or PaCO2 is raised. An early tracheostomy is useful since mechanical ventilation is likely to continue for several weeks. Patients w ith bulbar involvement or inadequate cough should have a tra- cheostomy even if spontaneous breathing continues. Cardiovascular care Continuous cardiovascular monitoring is required due to the effects of autonomic involvement. Arrhythmias are particularly likely with anaes- thesia (especially w ith suxamethonium). Hypertensive and hypotensive responses are generally exaggerated with v asoactive drugs. Nutritional support Parenteral nutrition will be required in cases where there is ileus. En teral nutrition is preferred if possible, but it should be noted that energy and \202 uid requirements are reduced in Guillain \200\223Barr syndrome. Analgesia Analgesia is required for muscle, abdominal, and back pain. Although NSAIDs may b e useful, opiates are often required. Other support Particular attention is required to pressure areas and deep vein throm- bosis prophylaxis. GUILLAIN \200\223BARR \211 SYNDROME 457 Key papers Plasma Exchange/Sandoglobulin Guillain-Barr Syndrome Trial Group. (1997) Rando mized trial of plasma exchange, intravenous immunoglobulin, and combined treatments in Guil lain-Barr syndrome. Lancet 349: 225 \200\22330. van Koningsveld R, for the Dutch GBS study group. (2004) Effect of methylprednisolone when added to standard treatment with intravenous immunoglobulin for Guillain-Barr syndrome: r an- domised trial. Lancet 363: 192 \200\2236. Hughes RA, Swan AV, Rapha l JC, et al. (2007) Immunotherapy for Guillain-Barr syndrome: a systematic review. Brain 130: 2245 \200\22357. See also: Airway maintenance, p40; Endotracheal intubation, p42; Ventilatory support \200 \224indications, p44; Plasma exchange, p114; Pulmonary function tests, p148; ECG monitoring , p162; Blood pressure monitoring, p164; Respiratory failure, p350; Hypotension, p380; Hype rtension, p382; Tachyarrhythmias, p384; Bradyarrhythmias, p386; Acute weakness, p440. 458 CHAPTER 27 Neurological disorders Myasthenia gravis \200 Myasthenia gravis is an autoimmune disease associated with acetylcholine receptor and, rare ly, anti-striated muscle antibodies. It is associated with autoimmune thyroid disease, SLE, and rheumatoid arthritis. Painless weakness with normal tendon re \202 exes, deterioratin g after exertion, and recovering after rest. Weakness deteriorates during stress, infection , or trauma. Younger (<45y), predominantly female patients may have a thymoma which, if res ected, may provide remission. Diagnosis of myasthenia \200 \200 