Eponymous signs \200 Kernig \200\231s sign: pain elicited on passive \202 exion of knees which represents nuch al sensitivity. Brudzinski \200\231s sign: neck \202 exion causing lower limb \202 exio n, especially in pediatric cases. Management The initial management of bacterial meningitis is to provide systematic support until an appropriate antibiotic regime has been implemented. However, in the initial phase of illness, bacterial and viral meningitis share many common features. In most circumstance s, a broad-spectrum Whilst commonly performed, many authors question the validity of these tests. 365 CHAPTER 22.3 Meningitis antibiotic regime to combat the suspected bacterial menin- gitis is commenced, based on epi demiological analysis of likely pathogens. (see above) analgesia. In some cases, including the immunocompro- mised, antiviral agents may be consid ered. Fungal meningitis Rare in the immunocompetent. Cryptococcus neoformans is the most common p athogen causing AIDS-related fungal meningitis. Treatment involves a prolonged course of an tifungals. Treatment Bacterial meningitis is a medical emergency and has a high mortality rate if untr eated. Following initial recognition, prompt senior intervention is required. Post-neurosurgical meningitis: The most common bacterial pathogens are staphylococci and Gr am-negative bacilli, especially in the presence of prosthetic material. Cephalosporins rema in ef \201 cacious treatment, dependent on local microbiological advice. If P. aeruginosa is isolated or suspected, Ceftazidime is pre- ferred. In those patients with resistant path ogens, vancomycin or chloramphenicol may be considered. Antimicrobial \200 Cephalosporins (2g Ceftriaxone or Cefotaxime) remain the \201 rst-line antimicrobial agen ts. Ampicillin 2g IV qds may be added in patients in whom Listeria monocytogenes is suspect ed (age <3 or >55yrs). Vancomycin may be required if pneumococcal penicil- lin resistanc e is considered likely. This may be changed on microbiological advice, once a pathogen has been identi \201 ed. Pediatric meningitis The management of meningococcal disease in pediatric patients requires early senior specialist pediatric and/or intensive care clinicians. A complete overview of the initial management is described by Pollard et al. Adjunctive Adjunctive treatment of bacterial meningitis with steroids have been proven to r educe its mortality and morbidity, including the rates of severe hearing loss and other neu ro- logical sequelae Some advocate the use of anticonvulsants and empirical antiviral thera pies. Public health considerations \200 Bacterial meningitis is a Noti \201 able Illness. Ensure that CCDC have been informed of l ikely/proven case to ensure prophylaxis can be considered for contacts. Isolation of the pa tient for the \201 rst 24h on admission is considered bene \201 cial. Notify microbiolog ical staff. Organ support Organ support via appropriate respiratory and cardiovas- cular treatment is m ost likely to be performed in a critical care environment. This may include: \200 Volume resuscitation isotropic or vasopressor sup- port in the presence of a systemic in flammatory response syndrome or shock Consider intubation and ventilation in refractory hyp oxia Consider tight glycaemia control, low dose corticoster- oid therapy and APC Correct el ectrolyte disturbances If signs of raised ICP treat with appropriate medical man- agement i ncluding ensuring control of PaCO2, 30 bed- head elevation, normothermia and the preventi on of seizures. Assess and treat sequelae. Further reading Beckham J, Tyler K. Initial management of acute bacterial meningitis in adu lts: summary of IDSA guidelines. Rev Neurol Dis 2006; 3: 57 \200\22360. \200 Hasbun R, Abrahams J, Jekel J, et al. Computed tomography of the head before lumbar punctur e in adults with suspected meningitis. N Engl J Med 2001; 345: 1727 \200\22333. \200 Pollard AJ, Britto J, Nadel S, et al. Emergency management of menin- gococcal disease in children. Arch Dis Child 1999; 80: 290 \200\2236. Nigrovic L, Kuppermann N, Malley R. Development and validation of a multivariable predictiv e model to distinguish bacterial from aseptic meningitis in children in the post-haemophilu s in \202 uenzae era. Pediatrics 2002; 110: 712 \200\2239. Prognosis Prognostic indicators of disease severity relate to the aeti- ology (bacterial, v iral, etc.) and the clinical \201 ndings, along with the development of complications. Ho lub et al. have proven the ef \201 cacy of CSF cortical levels as having prognostic predic tive value in bacterial meningitis. Provan D, Krentz A. Oxford handbook of clinical and laboratory investigation. Oxford: Oxford University Press. 2005. Thomas KE, Hasbun R, Jekel J, et al. The diagnostic accuracy of Kernig \200\231s sign, Brud zinski \200\231s sign, and nuchal rigidity in adults with suspected meningitis. Clin Infect Dis 2002; 35: 46 \200\22352. van de Beek D, de Gans J, McIntyre P, et al. Corticosteroids for acute bacterial meningitis . Cochrane Database Syst Rev 2007; (1): CD004405. Viral meningitis Viral meningitis is usually a self-limiting condition which responds to su pportive treatment, \202 uids, antipyretics and 366 M SMITH Intracerebral hemorrhage Investigations Cranial CT scan \200 \200 Intracerebral hemorrhage (ICH) is an acute spontaneous extravasation of blood into the brai n parenchyma. Urgent CT will con \201 rm the diagnosis of ICH The cause of the ICH may be suggested by t he pattern of bleeding The volume of the haematoma can be estimated Con \201 rmation of ex travasation of contrast into the hae- matoma predicts haematoma expansion Epidemiology \200 ICH accounts for 10 \200\22330% of all strokes but is one of the major causes of stroke-rel ated death and disability. >85% of cases of ICH occur as a primary event following spontane ous hemorrhage arising from rupture of small arteries and arterioles. The majority of prima ry ICH is associated with hyper- tension (60 \200\22370% of cases) or amyloid angiopathy (1 5% of cases). Around half of primary ICH occurs in the basal ganglia, one-third in the cere bral hemispheres and one-sixth in the brainstem or cerebellum. Secondary ICH is hemorrhage arising as a result of trauma, rupture of an intracranial aneurysm, an AV malformation or a coagulopathy. \200 MRI scan \200 \200 MRI is as sensitive as CT for acute detection of ICH Generally used as a follow-up study to identify AV mal- formation, amyloid angiopathy or associated neoplasm. Cerebral angiography \200 Angiography is useful for con \201 rming vascular causes of ICH such as AV malformation, d ural AV \201 stula, cortical vein thrombosis or vasculitis Angiography should always be c onsidered in young patients with no obvious risk factors for ICH. Incidence \200 \200 12 \200\22315 cases per 100 000 of the population More common in males, the elderly and in those of Asian and African ethnicity Incidence of ICH is signi \201 cantly increased in pa tients receiving antiplatelet or anticoagulation therapy. Management ICH should be treated as a medical emergency since delays in treatment are assoc iated with worse outcome \200\224the concept of \200\230time is brain \200\231 has recentl y been described Acute treatment includes airway management and control of blood pressure a nd ICP. Airway management is a prior- ity when conscious level is impaired in order to prot ect the airway and facilitate mechanical ventilation to minimize secondary brain injury fro m hypoxaemia and hypercarbia. Mortality after ICH is reduced in patients cared for in speci alist neurointensive care units. Risk factors Hypertension (especially untreated), cerebral amyloid angiopathy, high alcohol intake and cocaine use are risk fac- tors for ICH. The risk of antiplatelet drugs in gener al is unclear, but high-dose aspirin is associated with increased risk of ICH in the elderl y, particularly in the presence of untreated hypertension. Warfarin anticoagulation increas es the risk 5- to 10-fold. Cardiovascular control \200 Hypertension is common in the \201 rst 6h after ICH even in previously normotensive patie nts. Treatment of excessive hypertension should balance the risks of hypertension-related h aematoma expansion against excessive reduction in CPP and peri-haematoma ischaemia. Blood p ressure targets should be individualized but, in general terms, blood pressure should not b e treated unless >180/105mm Hg. In all cases SBP should be maintained >90mm Hg. Pathophysiology ICH was previously considered a single haemorrhagic event, but it is now kn own that it is a complex, dynamic process involving three distinct phases: (1) initial haem or- rhage, (2) haematoma expansion and (3) perihaematoma oedema. Two factors are of prime i mportance in disease progression and outcome. Haematoma expansion (often >33% original volu me) may occur for several hours after the onset of symptoms and is an important cause of ea rly neurological deterioration and a powerful predictor of adverse outcome. Peri-haematoma brain oedema starts early (in most cases within 3h from ICH onset) and evolves over many da ys. It occurs as a result of in \202 ammation, cyto- toxicity and blood \200\223brain barr ier disruption caused by release of thrombin and other coagulation end-products. Control of intracranial pressure Emergency measures to control ICP are required for comatos e patients or those who develop clinical signs of brainstem herniation. Medical management \200 Diagnosis ICH is usually associated with rapid onset focal neurologi- cal de \201 cit and signs of raised ICP such as vomiting and decreased level of consciousness. Severe ICH may r esult in immediate unconsciousness. More than 90% of patients present with acute hypertensi on (>150/100mm Hg). Dysautonomia, including hyperventilation, tachycardia, central fever an d hyperglycaemia, is also common. The dif- ferentiation between ICH and other forms of stro ke can- not be determined by clinical status alone and must be con \201 rmed by cranial CT or MRI scan. Standard methods of ICP control include 30 head-up tilt, mannitol or hypertonic saline. A lthough osmotic agents successfully reduce acute ele- vations in ICP, there is no evidence that they reduce mortality or disability after ICH. Neurosurgery \200 Neurosurgical intervention after ICH remains con- troversial The STICH (Surgical Trial in I ntracerebral Hemorrhage) trial showed no outcome bene \201 t of evacuation of a supratento rial haematoma within 72h of ICH. Although 367 CHAPTER 22.4 Intracerebral hemorrhage Large infused volumes may precipitate circulatory overload, and prothrombin complex concent rates may be used in patients in whom a large volume of FFP is contraindicated. rFVIIa is a promising candidate for the acute reversal of anticoagulation therapy but its short half-l ife is a drawback. However, evidence is currently limited and a controlled trial is needed. The optimal time for resumption of anticoagulation therapy after ICH has not been resolved . The risks and bene \201 ts of withholding or restarting treatment should be assessed for each patient individually. STICH challenges the view that early neurosurgery is an effective treatment for ICH, it doe s not con \201 rm that sur- gery is useless in all cases because patients who might have b ene \201 ted from emergency surgery were excluded from the study. Certain subgroups, such as younger patients with lobar hemorrhages causing signi \201 cant mass effect, might ther efore derive some bene \201 t from surgery. Furthermore, because the mean time to surgery was >24h, STICH does not exclude the possibility that ultra-early surgery might have a role in some patients. Patients with cerebellar hemorrhages >3cm in diameter bene \201 t from emergency surgical evacuation because of the high risk of early deterioration. Placement of an external ventricular drain may be life- saving in the presence of hydrocephalus. Other intensive care management \200 In addition to ventilatory support, blood pressure con- trol and ICP monitoring, general su pportive measures should be provided. Fever control is crucial since hyperthermia is associ ated with increased mortality and worse outcome in survivors. Seizures occur in 10% of pat ients after ICH, and EEG monitoring is recommended in those at particular risk (e.g. lobar haematoma). Seizures should be treated aggressively, but there is no evidence that prophyla ctic anticonvulsant therapy improves outcome. Tight glycaemic control is essential. ICH pat ients are at high risk for thromboembolic com- plications. Dynamic compression stockings an d intermit- tent calf compression should be initiated on admission to the ICU. SC heparin p rophylaxis is controversial, although there is some evidence that it is not associated with increased risk of intracranial bleeding. Calori \201 c intake should be maintained via th e enteral route whenever possible. Haemostatic therapy Recent evidence suggests that rapid correction of coagu- lopathy and en hancement of coagulation variables in the absence of coagulopathy can play a signi \201 ca nt role in the acute treatment of ICH and is associated with improved outcome. \200 The high incidence of early haematoma expansion, com- bined with the relationship between h aematoma volume and outcome after ICH, represents a potential target for acute therapeutic intervention. Recombinant activated factor VII (rFVIIa) is a potent initiator of haemostasi s approved for treatment of bleed- ing in patients with hemophilia resistant to factor VII replacement. In a preliminary study of 399 patients with ICH, rFVIIa administered within 4h of onset of symptoms reduced haematoma expansion by 50%, reduced mortality by 38% and impr oved functional outcome at 90 days. These bene \201 ts occurred despite a 5% increase in t he frequency of thromboembolic adverse events. The recently concluded phase III FAST study (Factor VIIa for Acute Hemorrhagic Stroke Treatment) con \201 rmed the ef \201 cacy of rF VIIa in controlling intracerebral bleed- ing and reducing haematoma volume but, in contrast to earlier studies, did not demonstrate a reduction in mor- tality or disability in surviv ors. There is some evidence from a post hoc analysis of the FAST data that rFVIIa might be effective in a subgroup of younger patients (<75yrs) when administered within 3h of onset o f symptoms. \200 Outcome \200 30 \200\22355% 6-month mortality overall, rising to 67% in patients receiving oral anticoag ulant therapy Predictors of mortality include large ICH volume, older age, coma, requiremen t for mechanical ventilation, intra- ventricular extension and posterior fossa hemorrhage. Fewer than 20% survivors regain functional independ- ence by 6 months. Further reading Diringer M, Edwards D. Admission to a neurologic/neurosurgical intensive ca re unit is associated with reduced mortality after intracerebral hemorrhage. Crit Care Med 2001; 29: 635 \200\22340. Reversal of anticoagulation Warfarin anticoagulation massively increases the risk of ICH, d oubles the mortality and increases the risk of pro- gressive bleeding and clinical deterior ation. Emergency reversal of oral anticoagulant therapy is recommended in warfarin-associat ed ICH despite the risks of thromboem- bolic complications. \200 \200 Marietta M, Pedrazzi P, Girardis M, et al. Intracerebral hemorrhage: an often neglected med ical emergency. Intern Emerg Med 2007; 2: 38 \200\22345. Mayer S. Recombinant activated factor VII for acute intracerebral hemorrhage. Stroke 2007; 38: 763 \200\2237. Mayer S, Rincon F. Treatment of intracerebral hemorrhage. Lancet Neurol 2005; 4: 662 \200\22372. Rincon F, Mayer, S. Novel therapies for intracerebral hemorrhage. Vitamin K should be administered immediately Coagulation factors should be given simultaneo usly as it takes several hours for vitamin K to achieve maximal effect. FFP should be infus ed until normal coagulation indexes are restored. FFP volumes between 800 and 3500ml may be required Curr Opin Crit Care 2004; 10: 94 \200\223100. 368 M SMITH Subarachnoid hemorrhage Aneurysmal subarachoid hemorrhage (SAH) is a neuro- logical emergency with a high rate of c omplications and death. Cerebral angiography \200 Four-vessel angiography is the gold standard for aneu- rysm identi \201 cation, characteri zation of vascular anatomy and diagnosis of cerebral vasospasm Conventional angiography is a time-consuming investiga- tion that is not risk free CT or MR angiography are non-invasiv e alternatives Epidemiology \200 SAH accounts for only 3% of all strokes but is one of the major cause of stroke-related dea th 80% of SAH is caused by a ruptured intracranial aneu- rysm Management Following SAH, cardiorespiratory status should be stabi- lized and patients tran sferred to a specialist neuroscience unit. Patients bene \201 t from multi-disciplinary ne urointensive care where management is targeted at optimizing cardio- vascular variables, se curing the ruptured aneurysm, detect- ing and treating intracranial complications, includin g the prevention and treatment of cerebral vasospasm, and man- aging systemic complications . Incidence \200 \200 6 \200\2238 cases per 100 000 of the population Peak incidence in the sixth decade of life Diagnosis SAH should be suspected in patients with sudden onset headache (often described a s the \200\230worst imaginable \200\231 or like a \200\230hammer blow \200\231), nausea, vomiting, photophobia and neck stiffness. Headache may be the only presenting feature in up to 40% of cases and may completely resolve within min- utes or hours (sentinel headaches). Sentinel headaches should be investigated urgently as they may proceed to a serious SAH wi thin 2 \200\2233 weeks. The diagnosis of SAH is more certain if the headache is accompanied by focal neu- rological signs, including third or sixth cranial nerve palsies, motor de \201 cits or obtunded conscious level. Catastrophic SAH presents as sudden loss of consciou sness. Cardiovascular control \200 Prior to control of the aneurysm, systemic blood pres- sure should be carefully controlled in the \200\230high normal \200\231 range to maintain cerebral perfusion whilst minimizing the risk of re-bleeding. Hypotension should be treated initially with IV \202 uids follo wed by vasopressors. Hypertension should only be treated if SBP exceeds 160mm Hg in a previ ously normotensive patient. Diagnosis SAH is initially misdiagnosed in up to 50% of cases. The differential diagnosis i ncludes migraine, tension headache and ischaemic or haemorrhagic stroke. Prevention of re-bleeding \200 Re-bleeding occurs in 7% cases and is prevented by early protection of the ruptured aneurys m Endovascular intervention is now the treatment of choice for the majority of aneurysms. E ndovascular treatment is associated with a relative risk reduction of 22.6% and absolute ri sk reduction of 6.9% in death or long-term dependency compared with surgical clipping. Grading of SAH Several grading scales have been developed to describe the severity of SAH a nd assess prognosis. That described by the World Federation of Neurosurgeons (WFNS) is wide ly used and based on the GCS and presence or absence of a motor de \201 cit. \200 \200 \200 \200 \200 Hydrocephalus \200 Grade 1: GCS 15 and no motor de \201 cit Grade 2: GCS 14 \200\22313 and no motor de \201 cit Grade 3: GCS 14 \200\22313 with motor de \201 cit Grade 4: GCS 12 \200\2237 with or wi thout motor de \201 cit Grade 5: GCS 6 \200\2233 with or without motor de \201 cit Hydrocephalus occurs in 25% patients within a few days after SAH. Temporary external ventr icular drainage may be indi- cated to relieve the hydrocephalus A minority of patients requ ire long-term CSF diversion via a ventricular shunt Investigations Cranial CT scan \200 Vasospasm With the current emphasis on early protection of ruptured aneurysms, cerebral vas ospasm and delayed ischaemic neurological de \201 cit (DIND) is the most common cause of m ortality and morbidity after SAH. Aggressive preventative and treatment strategies for vaso spasm are key compo- nents of the ICU management of SAH. Urgent CT scanning should be performed in any patient with suspected SAH Fine cut CT is ess ential since small blood loads can easily be missed Characteristic high density areas are s een in the basal cisterns and throughout the CSF spaces CT also demonstrates the presence o f cerebral oedema, hydrocephalus and intraparenchymal blood Pathophysiology \200 Vasospasm peaks at 4 \200\22310 days after the ictus and per- sists for several days. The e xact cause remains obscure but is related to blood load in the basal cisterns. Constituents of oxyhaemoglobin are likely spasmogenic factors, and several mechanisms co-exist, includi ng release of endothelin, generation of reactive oxygen species and inhibition of NO. Histo tological changes, including Lumbar puncture \200 LP should be performed in any patient with suspected SAH in whom the CT scan is equivocal o r negative Diagnostic features for SAH include high CSF opening pressure, elevated red cell count and xanthochromia after 12h. 369 CHAPTER 22.5 Subarachnoid hemorrhage Antiplatelet drugs reduce the risk of DIND with a trend towards improved outcome, but furth er studies are required to determine the haemorrhagic risk. There are con \202 icting data on the relative bene \201 ts and risks of LMWH after SAH. Antithrombotic agents are curre ntly only indicated in highly selected patients. adventitial in \202 ammation and intimal hyperplasia, also occur in the affected vessels. Diagnosis \200 Vasospasm is detected clinically in conscious patients by a reduction in conscious level wi th or without a focal neurological de \201 cit. Cerebral angiography is the gold standard for diagnosis of cerebral vasospasm. CT angiography is less invasive and may be combined wi th CT perfusion scanning to allow assessment of asso- ciated perfusion abnormalities Transc ranial Doppler ultrasonography is routinely used in the bedside assessment of vasospasm. Systemic complications Systemic complications occur in up to 79% of patients after SAH. and are independently associated with higher mortal- ity and worse functional outcome in survi vors. \200 ECG changes and \200\230stunned \200\231 myocardium syndrome are likely to be related to e ndogenous catecholamine release and activation of adrenoceptors. Pulmonary complications oc cur because of pulmonary expression of a systemic in \202 ammatory response, neuro- genic pulmonary oedema and as a complication of triple-H therapy. Hyponatraemia is common after S AH and related to haemodilution, cerebral salt wasting syndrome or the syndrome of inapprop riate antidiuretic hormone secretion. Fever, anemia and hyperglycaemia are associated with increased mortality and poor functional outcome in sur- vivors, and should be corrected. Prevention and treatment \200 Triple-H therapy (hypervolaemia, hypertension and haemodilution) is widely used to prevent and treat cer- ebral vasospasm after SAH. \200 Crystalloids and colloids should be infused (>3000ml/24h) to achieve a daily positive \202 uid balance Supranormal systemic blood pressure is maintained using vasopressors/inotr opes Haemodilution is the most controversial component of triple-H therapy and is not unive rsally applied Triple-H therapy is effective in reversing DIND in many patients but the ef \201 cacy of prophylactic treat- ment to prevent vasospasm is less clear Triple-H therapy is not a risk-free intervention and should be discontinued as soon as the DIND resolves. Outcome \200 \200 \200 SAH has an overall mortality rate of 51% 12% of patients die before they receive medical at tention 33% of survivors need lifelong care and a further 46% have residual cognitive de \201 cits that affect functional status and quality of life Prognosis depends on three fact ors \200\224the grade of SAH, the success of the procedure to secure the aneurysm and the o ccurrence of sequelae, particularly cerebral vasospasm, Endovascular treatments, including balloon angioplasty and intra-arterial infusion of vasod ilating agents, are use- ful in patients with symptomatic vasospasm resistant to triple-H t herapy. Cerebral protection Many pharmacological agents have been tested in clinical studies of SAH. Some have become e stablished into clinical practice whereas others show considerable promise. \200 Further reading Diringer MN. To clip or to coil acutely ruptured intracranial aneurysms: up date on the debate. Curr Opin Crit Care 2005; 11: 121 \200\2235. Nimodipine, a speci \201 c antagonist of the L-type voltage- gated calcium channel, improv es outcome after SAH and is administered routinely (60mg PO 4 hourly). Magnesium is a promi sing treatment, and small studies demonstrate a reduction in the incidence of DIND and impr oved outcome. Statins may reduce the incidence of vasospasm after SAH. Tirilazad has little effect on overall outcome after SAH but may have bene \201 t in patients with poor neurol ogical grade. Potential treatments include selective endothelin A receptor antagonists and PDE inhibitors. Gene therapy that targets the transcription of harmful protein products suc h as endothelin is also likely to be developed. Janjua N, Mayer SA. Cerebral vasospasm after subarachnoid hemorrhage. Curr Opin Crit Care 2003; 9: 113 \200\2239. Sen J, Belli A, Albon H, et al. Triple-H therapy in the management of aneurysmal subarachno id hemorrhage. Lancet Neurol 2003; 2: 614 \200\22321. \200 Smith M. Intensive care management of patients with subarachnoid hemorrhage. Curr Opin Anesthesiol 2007; 20: 400 \200\2237. Suarez J, Tarr R, Selman W. Aneurysmal subarachnoid hemorrhage. N Engl J Med 2006; 354: 387 \200\22396. Wartenberg KE, Mayer SA. Medical complications after subarach- noid hemorrhage: new strateg ies for prevention and management. Curr Opin Crit Care 2006; 12: 78 \200\22384. Wilson S, Hirsch N, Appleby I. Management of subarachnoid haemorhage in a non-neurosurgical center. Anesthesia 2005; 60: 470 \200\22385. Antithrombotic agents Microvascular thrombosis may contribute to DIND and, despite concerns about bleeding, there has been interest in the use of antithrombotic agents after SAH. \200 Cisternal infusions of recombinant tPA or urokinase are safe and effective interventions to reduce CSF blood load. 370 J ADCOCK Ischaemic stroke Introduction Stroke is the third most common cause of death world- wide and is a major caus e of disability. 85% of all strokes are ischaemic and, of these, 35% are due to large arter y throm- boembolism, 24% are caused by cardiac embolism (e.g. due to AF, mural thrombus pos t-MI or complicating endocarditis), 18% are due to small vessel disease, 18% are due to unc er- tain causes and 5% are due to rare causes (e.g. vasculitis, arterial dissection). The d iagnosis of ischaemic stroke requires a compatible history (an abrupt onset of a focal neur ological de \201 cit) and neurological examination (a neu- rological de \201 cit localize d to a vascular territory), with sup- portive evidence from neuroimaging (which also exclud es differential diagnoses such as tumor and hemorrhage), and blood testing to exclude hyper /hypoglycaemia, sepsis and other metabolic derangements. Some types of ischae- mic stroke c arry a particularly high mortality and morbid- ity rate, e.g. middle cerebral artery (MCA) with cerebral oedema and basilar thrombosis. There are now time-critical treatments availab le that improve outcome after stroke: aspirin and thrombolysis. Therefore, ischaemic stroke should be considered a medi- cal emergency. These treatments have resulted in a more aggre ssive approach to management, necessitating more active involvement of intensive care. Need for intensive cardiovascular monitoring \200 \200 Uncontrolled hypertension Myocardial ischaemia, congestive heart failure, arrhythmias In-ho spital strokes after medical and surgical procedures Need for general management \200 \200 \200 \200 Temperature control Glycaemic control Fluid management Treatment of complications, e.g. sep sis, pulmonary embolism Intubation for diagnostic or therapeutic procedures, e.g. MRI Acute treatment of ischaemic stroke Antiplatelet agents There is good evidence that use of aspirin (150 \200\223300mg/ day) commenced within 48h of the stroke reduces the risk of rec urrent stroke and death, as well as increasing func- tional outcome. Aspirin should therefo re be routinely commenced as soon as possible unless there is a clear con- traindication, s uch as proven ICH or de \201 nite aspirin sensi- tivity (e.g. wheeze or skin rash on aspir in exposure). Note, however, that protocols for the use of IV tPA call for avoid- ing all a ntithrombotic therapy, including heparin and aspirin, for the \201 rst 24h after thrombol ysis. Anticoagulation There is no proven bene \201 t from the routine use of antico- agula nts in the treatment of acute ischaemic stroke. Despite this, heparin is commonly used in p atients with cardioembolic stroke, large vessel stroke progression and basilar artery throm bosis. There is evidence, however, for anticoagulation for early secondary prevention in pa tients with cardiac embolism. In this circumstance, a delay of up to 2 weeks is recommended to reduce the risk of haemor- rhagic transformation, particularly in large strokes, before commencing heparinization and then warfarinization. There may be occasions where heparin m ay be appropriate, e.g. patients at high risk of thromboembolic disease, patients in AF or patients with stroke due to cerebral venous thrombosis. Aims of management in acute ischaemic stroke \200 \200 Identify diagnosis of ischaemic stroke Pay particular attention to onset time and vascular territory, e.g. MCA, basilar, posterior cerebral, lacunar syndrome Exclude hemorrhage (with CT) Consider other diagnoses, e.g. tumor, migraine, seizure, cerebral venous sinus thrombo sis, encephalitis Determine eligibility for thrombolysis Establish neurological status and blood pressure parameters Determine etiology and mechanism of stroke, e.g. carotid stenosis , AF, arteritis Prevent and treat complications Initiate secondary stroke prevention when a ppropriate, e.g. antiplatelet agents, cholesterol-lowering agents, blood pressure-lowering agents, carotid endarterectomy \200 \200 \200 Thrombolysis Reperfusion of ischaemic brain as soon as possible may lessen the volume of pe rmanently damaged brain and lead to a better clinical outcome. Thrombolytic therapy poten- tially improves perfusion by lysing the occluding thrombus. Thrombolytic therapy has now be en shown to reduce sig- ni \201 cantly the death rate and the number of patients left seve rely disabled after ischaemic stroke. There is, however, a net increase in deaths in the \201 rst 7 \200\22310 days from ICH. Three thrombolytic agents have been trialed: IV tPA (r ecombinant tissue plasminogen activator \200\224alteplase), intra-arterial prourokinase, an d ancrod (an IV de \201 brino- genating agent). tPA has been the most extensively investi- gated, and is associated with more bene \201 t and fewer risks. It is now approved for us e by NICE and US FDA. Importantly, there is a very narrow time rame for adminis- tration. T reatment must be instituted within 3h of a clearly de \201 ned time of onset of the ischae mic stroke (or the risk Suggested criteria for admission to ICU The following criteria are suggested for ICU admiss ion: \200 Need for monitoring neurological deterioration \200 \200 \200 \200 \200 \200 \200 \200 \200 Need for airway management \200 Maintain patient airway \200 Manage airway secretions/pneumonia Thrombolytic therapy Large hemispheric infarction Cerebellar infarction Basilar artery brai nstem stroke Fluctuating neurological de \201 cits Reduced conscious state Control of seiz ures Management of raised ICP Maintenance of CPP 371 CHAPTER 22.6 Ischaemic stroke of ICH outweighs the potential bene \201 ts of clot lysis). In the near future, however, n ew MRI techniques will be able to identify patients who might bene \201 t from treatment b eyond 3h. The patient must have a moderate to severe neurologi- cal de \201 cit without si gni \201 cant improvement. Absolute con- traindications include any blood on pre-treatment CT, established infarction on CT, severe hypertension, surgery or trauma within 14 days an d known coagulopathy. The NICE recommendations for administration are tPA infu- sion in a 0 .9mg/kg (max 90mg) continuous IV infusion over 60min, with 10% of total dose as a bolus at the start of the infusion (over 2 \200\2233min). These patients need careful moni- toring f or any neurological or cardiovascular decline, and should be managed in specialist units. F ollow-up CT scan should be performed after 24h, and aspirin should be com- menced if hemorr hage excluded. Other interventions The use of hyperventilation, steroids and mannitol to treat raised ICP and cerebral oedema in ischaemic stroke is widespread, although clinical trials do not demo nstrate improved survival or improved functional outcome Several potential neuroprotective agents have been studied, includ- ing calcium channel blockers, antioxidants and NMDA antag onists. Although trials have been completed, they are still of unproven clinical value. Res earch is currently ongo- ing into the potential bene \201 ts of therapeutic hypothermia. Other important stroke syndromes Cerebral venous sinus thrombosis Cerebral venous sinus thr ombosis should be considered as a cause of stroke in young women on the oral contracep- tiv e pill, during pregnancy and puerperium, in association with intracranial, ear or sinus inf ections, in patients with cancer and hematological disorders, and in patients with other ty pes of hypercoaguable states, such as in \202 ammatory bowel disease, phospholipid antibod y syndrome or severe dehydration. Headache and seizures are common, and should alert to the possible diagnosis. Papilloedema with focal neurology is not uncommon. MRI with MR venogra - phy or CT with CT venography are the investigations of choice to con \201 rm the diagnos is. Formal angiography may also be required, particularly in a patient with smaller vein oc clusions. Many centers recommend anticoagulation with heparin and then warfarin, although s upportive evidence from randomized trials is lacking. Causes of late deteriora- tion includ e extension of the thrombosis, raised ICP, seizures, systemic complications (pneumonia, PEs , sepsis) and complications of the associated hypercoaguable state. Intra-arterial tPA There are theoretical advantages to using intra-arterial tPA compared wi th systemic administration. Local tPA may be safer and more effective, as a higher concentr ation of tPA is attained directly at the thrombus site with potentially minor systemic side effects. However, intra-arterial throm- bolysis is limited to specialized centers. There a re only a few small randomized trials addressing this technique, but there is evidence for ef \201 cacy in acute basilar occlusion. Acute basilar occlusion accounts for up to 10% of large- vessel stroke, with the fatality rate being the highest for all ischaemic stroke su btypes, up to 90%, with rapid progres- sion to coma and death in many patients. Although no large randomized studies have been performed, there is evi- dence from small series that p atients who undergo suc- cessful recanalization of the basilar artery by intra-arterial thr ombolysis have lower mortality of 39%. There have also been some case reports of recanaliza tion by intra-arterial thrombolysis up to 18h after the onset of the basilar occlu- sion wi th improved outcome. Support groups The Stroke Association: www.stroke.org.uk American Stroke Association: www.s trokeassociation. org Decompressive surgery There are certain circumstances where neurosurgical intervention may be considered. Decompressive surgery involves the removal of a large part of the skull to a llow space for the expansion of swollen brain tissue, which thereby reduces ICP, prevents f atal brain herniation, increases perfusion pressure to the brain that is still salvageable, and preserves CBF. Patients with large supratentorial infarcts may deteriorate due to mass ive cerebral oedema, usually developing between 2 and 5 days. Recent pooled data from three ran- domized trials has demonstrated that in patients with malignant MCA infarction, decom pressive surgery under- taken within 48h of stroke onset reduces mortality and increases th e number of patients with a favorable func- tional outcome, particularly if the non-dominan t hemi- sphere is involved. The decision to perform decompressive surgery should, however, be made on an individual basis in every patient Large cerebellar infarctions may be associa ted with oedema, which can cause compression of the 4th ventricle, obstructive hydrocephalu s, herniation and death. Therefore, cerebellar infarction associated with a declining level of consciousness constitutes a potential neurosurgical emergency. Surgical decompression o f the posterior fossa or shunting may be required. As the level of consciousness is the mos t powerful predictor for outcome, patients with large cerebellar infarction should be obser ved on a stroke unit or ICU. Further reading Chen, ZM, Sandercock P, Pan HC, et al. on behalf of the CAST and IST Collab orative Groups. Indications for early aspirin use in acute ischaemic stroke: a combined ana lysis of 40,000 randomized patients from the Chinese Acute Stroke Trial and the Internation al Stroke Trial. Stroke 2000; 31: 1240 \200\2239. Gubitz G, Counsell C, Sandercock P, et al. Antiplatelet agents for acute ischaemic stroke. In: The Cochrane Library. Oxford: Update Software, 2000a. Gubitz G, Counsell C, Sandercock P, et al. Anticoagulants for acute ischaemic stroke. In: T he Cochrane Library. Oxford: Update Software, 2000b. Kollmar R, Schwab S. Ischaemic stroke: acute management, inten- sive care, and future persp ectives. Br J Anaesth 2007; 99: 95 \200\223101 National Institute for Health and Clinical E xcellence. Final appraisal determination: alteplase for the treatment of acute ischaemic st roke. Issue date April 2007, www.nice.org.uk Singh V. Critical care assessment and management of acute ischae- mic stroke. J Vascul Intervent Radiol 2004; 15: S21 \200\2237. Smith WS. Intra-arterial thrombolytic therapy for acute basilar occlusion. Stroke 2007; 28: 701 \200\2233. Vahedi K, Hofmeijer J, Juettler E, et al. Early decompressive surgery in malignant infarcti on of the middle cerebral artery: a pooled analysis of three randomized controlled trials. Lancet Neurol 2007; 6: 215 \200\22322. Wardlaw JM, del Zoppo G, Yamaguchi T, et al. Thrombolysis for acute ischaemic stroke. Cochr ane Database Syst Rev 2003; (3): CD000213. Warlow CP, Dennis MS, van Gijn J, et al. Stroke: a practical guide to management, 2nd edn, Oxford: Blackwell Science, 2001. 372 M SMITH & C PRITCHARD Guillain \200\223Barre syndrome Clinical features GBS is preceded by a \200\230 \202 u-like illness or gastroenteritis in 66% of cases. A symmetrical weakness evolves over a few days, usually after the antecedent symptoms have settled. Sensory symptoms and pain may pre-date the onset of weakness. The w eakness reaches a peak within 2 \200\2234 weeks and, following a plateau phase lasting 3 \200\2234 weeks, resolves over a variable period.