356 Table 10.10 Causes of vertigo Vestibular end organs and vestibular nerve M ni re \200\231s disease Vestibular neuronitis (acute labyrinthitis) Benign position al vertigo Motion sickness Trauma Ototoxicity (aminoglycosides) Herpes zoster oticus (Ramsa y-Hunt syndrome) Brainstem, cerebellum, and cerebellopontine angle MS Infarction/transient ischemic attack (TIA) Hemorrhage Migraine aura (basilar-type, uncom mon) Vestibular schwannoma (acoustic neuroma) Cerebral cortex Vertiginous epilepsy Alcohol or other intoxication Migrainous vertigo Cervical vertigo (con troversial; neck symptoms are more commonly a result of a patient keeping the neck stiff to avoid exacerbating vertigo) Deafness Simple hearing tests To establish a clinical finding of hearing loss, the examiner should whisper a number increasingly loudly in one ear while blocking the other ear with a finger. The patient is asked to repeat the number. Make sure that failure is not due to mi sunderstanding. Rinne \200\231s test Place the base of a vibrating 256 (or 512) Hz tuning f ork on the mastoid process. When the patient no longer perceives sound, move the fork so th at the prongs are 4 cm from the external acoustic meatus. The energy in the fork will be le ssening, but the sound will be heard again if air conduction (AC) is better than bone condu ction (BC), as in the normal situation. If on the other hand, BC > AC, there is either cond uctive hearing loss or a false-negative result due to sensorineural deafness with \200\234h earing \200\235 of sound in the other ear. Distinguish these possibilities with Weber \200 \231s test (below). If there is hearing loss and AC is better than BC, this suggests sensor ineural deafness. Weber \200\231s test Place a vibrating tuning fork in the middle of the f orehead. Ask which side the patient localizes the sound to \200\224or is it heard in the mi ddle? In unilateral sensorineural deafness, the patient will localize the sound to the good side. In conduction deafness, the sound is located to the bad side (as if the sensitivity of the nerve has been turned up to allow for poor AC). Neither of these tests is completely reliable. Conductive deafness Mechanical in nature, usually due to wax, otoscle- rosis, or otitis media. Causes of sensorineural deafness Due to dysfunction of the cochlea or the au ditory nerve. Presbycusis (senile deafness, typically higher frequen- cies); previous noise exposure; M ni re \200\231s disease (lower frequency); menin- gitis; acute labyrinth itis; head injury; acoustic neuroma; MS (rarely); Paget \200\231s disease; ototoxic drugs, such as aminoglycosides; autoimmune disorders or vasculitides; maternal infections during p regnancy; several rare congenital syndromes. Brain MRI can assess for AICA strokes, masses or lesions of the eighth nerve, and the MS-like lesions seen in Susac \200\231s syndrome, a vasculitis that presents with sensorineural hearing loss, branch retinal artery occlusions (BRAO, best identified on fluorescein angiography), and focal CNS symptoms. y g o o r u e N l 357 Tinnitus This symptom is the perception of ringing, buzzing, or other noises gener- ally wi thout external sound. It is a common phenomenon. In most cases, the sound is an illusory su bjective perception of a high-pitched whine, but there are conditions where there is object ively measurable sound. Causes Unknown, hearing loss (20%), wax, viral, presbyacusis, noise (e.g., gunfire), head injury, suppurative otitis media, post-stapedectomy, M ni re \200\231s (often lower pitched/hissing/roaring/staticky), head injury, anemia, hyper- tensi on (found in up to 16%, but it may not be causative). Drugs: Aspirin or other salicylates, loop diuretics, aminoglycosides (e.g., gentamicin). Causes of pulsatile tinnitus: i.e., wit h heartbeat; potentially audible with stethoscope; do MRI. Carotid artery stenosis/dissecti on, arteriovenous (AV) fistula, glomus jugulare tumors, radiating cardiac murmur, elevated intracranial pressure, dehiscence of temporal bone near a branch of the carotid. Treatment Identify and treat the underlying pathology if possible. Specific treatments for tinnitus i tself are often unsatisfactory and may involve the use of masking hearing devices or white- noise and behavioral conditioning. Abnormal movements Dyskinesia (abnormal involuntary movements) Tremor Rest tremor is rhythm ic, present at rest during waking, and abolished on voluntary movement. It occurs in parkin sonism (with rigidity/bradykinesia) and may respond to dopaminergic medications. Intention tremor is an irregular, large-amplitude shaking worse on reaching out for something, typica lly more dramatic the closer the movement is to the target. It is typical of cerebellar dis ease (e.g., MS). Medical treatment is difficult; use of wrist weights or extra-heavy utensi ls may improve function- ing by dampening the oscillations. Some patients may benefit from thalamic deep brain stimulation. Postural tremor is absent at rest, present on maintained p osture (e.g., arms outstretched), and may persist (but is not exaggerated) on movement. Cau ses: Familial essential tremor (autosomal dominant; improved with alco- hol, \222 -blocker s, primidone, or, in severe cases, with deep brain stimulation), thyrotoxicosis, anxiety, c affeine or other stimulants, withdrawal from alco- hol or benzodiazepines. Chorea, athetosi s, and hemiballismus Chorea: Nonrhythmic, jerky, purposeless movements that flit from one p art of the body to another. Causes include Huntington \200\231s and Sydenham \200\231s chor ea (choreoathetoid movements) \200\224a rare complication of streptococcal infection. Chore a gravi- darum is a poorly understood condition typically self-limited to pregnancy. The an atomical basis of chorea is uncertain but it is thought of as the phar- macological mirror image of Parkinson \200\231s disease (PD) (levodopa worsens chorea). Hemiballismus: Large-a mplitude, flinging hemichorea (affects proxi- mal muscles) contralateral to a lesion of the subthalamic nucleus (often a lacunar infarction in an elderly diabetic). Recovers spontane ously over months. Athetosis: Slow, sinuous, confluent, purposeless writhing move- ments (e specially of the digits, hands, face, tongue), often difficult to dis- tinguish from chorea (some consider chorea-athetosis a continuum). Most common cause is cerebral palsy. Treatme nt of these adventitious movement disorders is difficult, but recently tetrabenazine has be en shown to improve function in Huntington \200\231s, although with a significant risk for depression. Tics Brief, repeated, stereotyped movements that patients are able to vol- unta rily suppress for a time, at least until an overwhelming urge \200\234builds up \200\235 th at is released by the acting out of the movement. Simple tics are common in children, but u sually resolve. In Gilles de la Tourette \200\231s syndrome , multiple motor and vocal tics occur. Consider psychological support; the central 2 agonists clonidine or guanfacine a re first-line treatments, and various antipsychotic agents may be required if tics are seve re. Myoclonus Sudden involuntary focal or general jerks arising from cord, brainstem, or ce rebral cortex, seen in neurodegenerative disease (e.g., lyso- somal storage enzyme defects) , Creutzfeldt-Jacobs disease (CJD), myoclo- nic epilepsies (including infantile spasms), an d sometimes post spinal cord injuries. Most commonly, multifocal or generalized myoclonus i s seen in severe toxic or metabolic disturbances, such as hepatic, renal, or ventilatory in sufficiency, or due to medications such as cephalosporins. Benign essen- tial myoclonus: Ge neral myoclonus begins in childhood as muscle twitches (autosomal dominant and has no other consequences). Asterixis: Can be considered a negative myoclonus, the loss of muscle tone. Seen as down- ward \200\234flap \200\235 of outstretched hands from loss of extensor tone . Myoclonus may respond to valproate, levetiracetam, or clonazepam. Post-anoxic If seen in a comatose patient after circulatory arrest, prognosis is usually fatal. In post-respirator y arrest (e.g., asthma), survivors may exhibit a stimulus- or 358 action-induced myoclonus, known as the Lance-Adams syndrome. Cause is thought to be selecti ve vulnerability and loss of Purkinje cells. Dystonia Prolonged muscle contraction causing abnormal posture or repetitive movements due to any number of causes. Dystonia may worsen i n conditions of mental or emotional stress. In patients <40 with wide- spread dystonia, con sider a trial of levodopa to rule out dopa-responsive dystonia (rare), a genetic disorder. Many patients with dystonia suffer from mutation of the DYT-1 gene. Some dystonia patients respond to high-dose trihexyphenidyl or deep brain stimulation. Cervical dystonia, or spasm odic torticollis, is relatively common, a focal dystonia of the neck musculature resulting in a head tilt or \200\234wry neck. \200\235 Blepharospasm , involuntary con- traction of orbicularis oculi, and writer \200\231s cramp are other focal dystonias. Disabling focal dy stonias may respond to botulinum toxin injected into the overactive muscles. Acute dystonia may occur in young men starting neuro- leptics (head pulled back, eyes drawn upward, trism us). Use anticholinergics (benztropine 1 \200\2232 mg IV). Tardive dyskinesia Involuntary c hewing and grimacing movements, a dreaded complication due to long-term use of neuroleptic agents (e.g., antipsychotics such as haloperidol or antiemetics such as metoclopramide or p rochlorperazine). Treatment: Withdraw neuroleptic and wait 3 \200\2236 months. The dyskines ia may fail to resolve or may even worsen. If so, con- sider tetrabenazine 25 \200\22350 mg /8 h. y g o o r u e N l Ischemic stroke Stroke: Clinical features and investigations Strokes result from ischemic i nfarction or bleeding into part of the brain, manifest by rapid onset (instantly, or over m inutes) of focal CNS signs and symptoms. It is the major cause of permanent neurological di sability and death. Incidence: There are 700,000 strokes each year in the United States. It is the third leading cause of death behind heart disease and cancer. Causes: \212 \212 Thrombosis-in-situ Heart emboli (atrial Table 10.11. Atherothromboembolism (often from caro tids) Ischemia due to hypoperfusion distal to an intracranial stenosis CNS hemorrhage (hype rtension, trauma, cocaine use) 359 fibrillation, infective endocarditis, MI). See \212 \212 \212 Rare causes: Sudden hypotension ( \200\234watershed infarctions \200\235 in distal perfu- sion territories), vasculitis, venous sinus thrombosis. In young patients sus- pect: Thrombophilia, vasculitis, venous-sinus thrombosis, carotid artery dissection (s pontaneous or from neck trauma or fibromuscular dysplasia), cardiac defects. Risk factors H ypertension, smoking, diabetes mellitus, heart disease (val- vular, ischemic, atrial fibril lation), peripheral vascular disease, prior TIA or stroke, carotid bruit, hyperlipidemia, e xcess alcohol, hypercoagulable states. Signs Sudden onset or a step-wise progression over m inutes to hours is typical. In theory, focal signs relate to distribution of the affected a rtery, but collateral supplies can cloud the issue. Cerebral hemisphere infarcts (50%) may cause contralateral hemiplegia that is initially flaccid (floppy limb, falls like a dead we ight when lifted), then over days to weeks becomes spastic (UMN); contralateral sensory los s; homonymous hemianopia; dysphasia. Brainstem infarction (25%) produces a wide range of effects that include quadriplegia, dist urbances of gaze and vision, locked-in syndrome (aware, but unable to respond), ataxia, ver tigo, and possibly dysphagia. Lacunar infarcts (25%) are small infarcts around basal gangli a, internal capsule, thal- amus, and pons. Classically, they may cause pure motor, pure sen sory, mixed motor and sensory signs; ataxia with hemiparesis; or dysarthria with a clumsy h and. Cognition and cortical functions remain intact. Evaluation of acute strokes The approa ch to emergent stroke manage- ment has changed dramatically with the advent of thrombolytic therapy. In most cases, the following steps are undertaken, potentially in parallel: \212 \212 \212 \212 \212 Stabilize patient Establish diagnosis Establish time of onset Grade severity Begin acute th rombolytic therapy: \212 \212 \212 Begin peristroke assessment and management Prevent an d treat acute post-stroke complications Modify secondary risk factor Rehabilitate Establish eligibility Establish contraindications Administer if appropriate \212 \212 \212 \212 Establishing the diagnosis of ischemic stroke and the time of onset has become critical for identifying patients who could benefit from the IV or intra-arteri al administration of thrombolytics. Thus, the evaluation of a patient presenting with new-o nset stroke symptoms includes the follow- ing: stabilization (the ABC \200\231s of airway, breathing, circulation), evaluation of vital signs, assessment of blood glucose (as hypo- a nd hyperglycemia can cause focal neurologic deficits), a thorough history and physical, and a noncontrast CT scan of the brain to rule out intracranial hemorrhage. Patients presentin g early enough (such that a workup can be completed and therapy initiated within 3 h or, in certain cases, 4.5 h of onset of symptoms) and meeting inclusion criteria without exclusio n criteria are candidates for modestly effective IV thrombolytic therapy. If the patient pr esents in such a way that therapy cannot be administered within 3 \200\2234.5 h of symptom onset, then consideration may be given for intra-arterial thrombolysis or clot retrieval (i f administration will occur within 6 h of symptoms, or longer in posterior circulation case s). Diffusion-weighted MRI imaging (DWI) has dramatically improved the detection of early a nd small strokes and the ability to distinguish stroke from mimics, with high sensitivity a nd specificity (Figure 10.5). Additional MRI techniques (comparing perfusion deficits to ar eas of infarction on DWI, for example) may eventually allow for a longer time window in pat ients with a small central area of infarction but a much larger territory at risk of ischem ic death. After the acute management stage \200\224which also involves ensuring adequate sw allowing, nutrition, and treatment of complications such as pneumonia and prophylaxis again st deep vein thrombosis (DVT) \200\224physicians need to pursue appropriate evaluations to identify modifiable patient risk factors for future strokes. These tests are meant to impro ve secondary prevention. They include evaluations for: \212Hypertension: Look for retinopa thy and enlarged heart on chest x-ray (CXR). Acutely raised BP is common in early stroke. I n general, do not treat the elevated pressure acutely. This elevation of BP may be respon- sible for collateral flow to \200\234at risk \200\235 but not yet infarcted brain tissue (t he so-called ischemic penumbra). Once the patient is out of the acute 360 post-stroke period, tight BP control, typically with a thiazide diuretic or an angiotensin- converting enzyme (ACE)-inhibitor is a mainstay of sec- ondary prevention). y g o o r u e N l \212Cardiac source of emboli: Atrial fibrillation (AF): Emboli from the left atrium may ha ve caused the stroke. Look for an enlarged left atrium (ECG, CXR, echo). Post-MI: Mural thr ombus is best seen by echocardiography. In stroke from AF or mural thrombus, do CT to exclu de a hemorrhagic stroke, then start aspirin; wait before commencing full anticoagulation to avoid bleeds into infracted brain tissue. SBE/IE: 20% of patients with bacterial endocardi tis present with CNS signs due to septic emboli from valves. Anticoagulation in such cases can potentially lead to disastrous complications from bleeding mycotic aneurysms and must b e balanced against risk of clotting from a mechanical valve (if present). Treat as endo- ca rditis; seek input from both neurology and cardiology. \212Carotid artery stenosis: In carotid territory stroke/TIA, randomized trials show clear benefit of carotid endarterectomy or stenting, so expert bod- ies affirm that 80% stenosis (on Doppler ultrasound) merits angiography interventions in appropriate patients. Table 10.11 Cardiac causes of stroke Cardioembolic causes are the source of stroke in >30% of patients in population studies. If identified, cardioembolic sources can dramatically change secondary prevention strategies. \212 Atrial fibrillation (AF) \206\221 risk of stroke fivefold (5 \200\22312% per year, depend- ing on comorbidities). This risk rises with age, duration of AF, hyper- tension, and heart failure \200\224and if the AF follows rheumatic fever. Left ventricular dilatation, left a trial enlargement with stasis, and mitral valve disease particularly increases risk for str oke; this risk can be largely reduced by anticoagulation. Aspirin may be preferable for tho se at low risk of stroke (<65, no concurrent vascular risk factors, no history of cerebral events), or for those with high risk of hemorrhage. Aim for an International Normalized Rat io (INR) of 2.0 \200\2233.0 (stroke risk is twice as much for those with an INR of 1.7 as o pposed to 2). Newer non-warfarin anticoagulants (e.g., dabigatran, rivarobaxan, apixaban) h ave been developed. They generally do not require thera- peutic monitoring, but lack of rev ersibility, which may be a serious issue in the event of acute intracranial hemorrhage or o ther bleeding complication. Although they do have their own issues in terms of spe- cific d rug interactions and use in hepatic or renal failure, it is possible that one or more may e ventually prove superior to warfarin. Studies of extended-wear cardiac telemetric or event monitors have shown a significant proportion of otherwise cryptogenic strokes may be caused by otherwise asymptomatic paroxysmal atrial fibrillation and should be considered in such cases. External cardioversion is complicated in 1 \200\2233% by peripheral emboli: Pharmaco logical cardioversion may carry similar risks. Prosthetic valves risk major emboli; anticoa gulate (INR 2.5 \200\2233.5). Acute myocardial infarct with large left ventricular wall mot ion abnor- malities on echocardiography predispose to left ventricular thrombus. Emboli ari se in 10% of these patients in the next 6 \200\22312 months; risk is reduced by two-thirds by anticoagulation. Paradoxical systemic emboli via the venous circulation in those with pa tent foramen ovale and atrial and ventricular septal defects can occur. 361 \212 \212 \212 \212 \212 \212 Figure 10.5 Diffusion-weighted MRI of brain revealing right sided, MCA territory infarct The treatment of stroke will vary somewhat depending on the etiol- ogy, but in almost all c ases patients will be started on an antiplatelet agent (aspirin), a statin, and possibly a thiazide diuretic, ACE-inhibitor or angiotensin receptor blocking agent. DVT prophylaxis is indicated during hospitalization and rehabilitation. Dysphagia screens for anyone with fac ial weakness or cognitive impairments should be done on ad- mission to identify patients at increased risk for aspiration. Based on numerous large studies, there is no indication for empiric anticoagulation or \200\234heparinization \200\235 in stroke patients. The additio n of heparin in all stroke patients seems to help as many individuals as it harms, making i ts \200\234stan- dard \200\235 use impractical and unwarranted. \212Diabetes mellitus: Stroke in the setting of elevated blood glucose may have worsened o utcome. Tight control of blood sugar from immediately after stroke is recommended for initi al outcome as well as secondary prevention. 362 \212Hyperlipidemia: Acute, high-dose statin (HMG-CoA reductase inhibitor) therapy has been shown to reduce risk in myocardial infarction; many neurologists take the same approach pr esumptively in stroke. Statins reduce risk of second stroke, probably even in the absence o f significant hypercholesterolemia. \212Giant cell arteritis: If ESR is extremely elevated or there is a history of subacute h eadache, tender scalp (not necessarily temporal), or symptoms consistent with polymyalgia r heumatica, give steroids promptly, then biopsy within 10 d. \212Syphilis: Look for active, untreated disease. Central retinal artery occlusion (CRAO) is an ophthalmological emergency that should be considered as a stroke of the retina. It pr esents with sudden, painless monocular visual loss and an often initially bland fun- duscop ic exam with an afferent pupillary defect (positive swinging flashlight test). Promptly adm inistered systemic or catheter-directed thrombolytic therapy may prevent permanent blindnes s (the time window for admin- istration may extend to 24 hours, the but earlier the better) . Giant cell (temporal) arteritis must be on the differential diagnosis of causes, along wi th carotid and embolic disease. Transient ischemic attack The sudden onset of focal CNS signs or symptoms due to temporary occlu- sion, usually by emboli, of part of the cerebral circulation, is termed a TIA if sym ptoms fully resolve within 24 h (TIAs are typically much shorter, resolv- ing in far less t han an hour) and there is no subsequent evidence of infarct on MRI. As vascular events, the y are the harbingers of impending stroke or even MI. If they are recognized for what they a re and preventive measures are prompt, a disastrous infarction may be averted. Simple scori ng systems such as ABCD 2 (see Table 10.12) have been developed that may predict risk of su bsequent stroke and facilitate triage in terms of the need for expedited workup (older pati ents, those with hypertension or diabetes, or those with long duration symptoms). It cannot be strongly enough emphasized that it is much better to prevent a stroke than to treat one after it has occurred. Whereas TIA is a warning shot across the bow, a stroke is a sinking ship. Symptoms Attacks may be single or many. Symptoms may be the same or different on eac h occasion and depend on the specific arterial terri- tory involved. Symptoms are sudden on set and typically last <30 minutes. Anything that lasts >2 hours or so will often be reveal ed by subsequent MRI imaging to involve infarction of tissue, even in cases of near complet e improvement. In carotid disease, in addition to the expected contralat- eral weakness/num bness and higher cortical function deficits (dominant: Language; nondominant: Neglect or vi suospatial problems) be alert for amaurosis fugax (one eye \200\231s vision is blotted out \200\234like a curtain descending over my field of view \200\235), representing a transien t occlusion of the ophthalmic artery (the first branch of the internal carotid). Signs No C NS signs 24 h after an attack . Listen for carotid bruits, although their absence does not rule out a carotid source of emboli. Tight stenoses often have no bruit. Listen for cardiac murmurs suggesting valve disease and identify AF. Causes The same as for ischemic stroke. Differential diagnosis of brief, focal CNS symptoms: Migraine aura (symptoms spread and int ensify over minutes, typically involving both positive and negative phenomena, as opposed t o TIA in which symptoms are negative only); focal seizure (symptoms typically spread over s econds and often include twitching and jerking). Any episodic cause of dizziness y g o o r u e N l 363 Table 10.12 ABCD 2 score for risk of stroke after tia Points Age of Pt <60 BP Clinical Features Duration Diabetes 0 Normal Other below speech distur- bance w/o weakness than <10 mins No DM 1 \211 60 \211 140/90 10 \200\22359 mins DM present 2 unilateral weakness \211 60 mins ABCD 2 score: 1 \200\2233 (low) 1.0% 1.2% 4 \200\2235 (mod) 4.1% 5.9% 6 \200\2237 (high) 8.1% 11.7% 2 day risk 7 day risk (see above) may to some extent mimic vertebrobasilar insufficiency. Sometimes the problem l ies in the peripheral nerves. Rare mimics of TIAs: Malignant hypertension , hypoglycemia , MS , intracranial lesions , somatization . Tests TIAs should be urgently evaluated in a man ner similar to acute strokes. An inpatient admission should be considered if the TIA was re cent, given the 12% rate of stroke within 30 d following a TIA, perhaps utilizing additiona l information based on ABCD 2 or similar scoring. Treatment Treat exactly as if the patient has had a true ischemic stroke but made a full recovery, with appropriate secondary stroke prevention measures. Intracerebral hemorrhage 10 \200\22320% of all strokes are hemorrhagic. The pathophysiology and man- agement of hemorrhagic strokes are completely different from ischemic strokes, ye t initial clinical presentations can be identical. Thus, it is impera- tive that all patien ts presenting with symptoms of an acute stroke rap- idly undergo brain imaging \200\224typi cally a noncontrast head CT \200\224to quickly diagnose intracerebral hemorrhages (ICH). Hy pertension, drug use, head trauma, and vascular malformations are risk factors for ICH, wit h hyperten- sion being the most common cause of spontaneous intracerebral hemor- rhage. Com mon locations of hypertensive ICH include the basal ganglia, thalamus, and cerebellum. Loba r or cortical hemorrhages should prompt a search for another underlying lesion or amyloid d isease. The treatment of patients with ICH begins with evaluation of the airway, breathing, and cardiovascular status. If the patient is stable, then directed therapy for the hemorrh age is initially focused on preventing expansion of the hematoma. Two factors, if left unco ntrolled, can lead to dramatic worsening of the patient \200\224hypertension and coagulopat hies. Patients who present with an ICH and elevated BP should have a careful but rapid redu c- tion in their BP following the guidelines used to treat hypertensive emergen- cies. If t he patient is known to be on anticoagulation, has a known bleeding disorder, or has coagula tion profiles that are noted to be abnormal, then transfusion with fresh frozen plasma shou ld be instituted (specific coagul- opathies or drugs can be treated differently). There are various scales prognosticating functional outcome after ICH. In general, patients with lar ger intracerebral hemorrhages, unstable vitals at presentation, diminished level of conscio usness (as measured by the Glasgow Coma Scale), and the presence of intraventricular extens ion do much worse. If patients survive the initial hemorrhage and do not suffer further ble eding, then the outcome will dictated by the amount of \206\221 ICP and tissue damaged. Ne wer studies suggest that catheter-directed throm- bolytic therapy into the ventricles or ev en into the clot itself may improve outcomes. 364 Subarachnoid hemorrhage Spontaneous arterial bleeding into the subarachnoid space is often a cata- strophic event and always a neurological emergency. Incidence 8/100,000/yr; typical age: 35 \200\22365. Causes Rupture of saccular aneurysm is the most common cause (80%), wi th arteriovenous malforma- tions accounting for 15%. An underrecognized condition known as revers- ible cerebral vasoconstriction syndrome (RCVS) may be responsible for focal, corti cal subarachnoid hemorrhage (SAH), particularly when present- ing as thunderclap headache. Benign venous events may be the cause of small perimesencephalic SAH. Associations: Smoking , hypertension, alcohol abuse, bleeding disorders, mycotic aneurysm, postinfective endocarditis. Lack of estrogen ( postmenopausal) has also been implicated. Genetics: Close relatives of those with SAH have a 3 \200\2235-fold increase in risk for SAH. Berry aneurysms Common sites: Junction of the posterior communicat- ing with the internal carotid (or of the anterior communicating with the anterior cerebral) or bifurcation of the middle cerebral artery. 15% are mul- tiple. So me are hereditary. Skin biopsy may reveal type 3 collagen deficiency and identify relatives at risk. Associations: Polycystic kidneys, coarctation of the aorta, Ehlers \200\223Danlos syndrome (hypermobile joints + \206\221 skin elasticity), fibromuscular dysplasia. Clinic al seconds) devastating \200\234thunderclap \200\235 headache \200\234The worst headache o f my life, \200\235 often occipital. Vomiting, collapse ( seizures), and coma frequently follow. Coma/drowsiness may last for days. Up to 15% of patients die by the time they reach the hospital; overall mortality at 6 months is near 50%, and one-third or so of survivors will have residual neurological deficits (mor- tality risks at presentation are given in Ta ble 10.13). Signs: Neck stiffness; retinal and subhyaloid hemorrhage; or focal neurologic f indings, particularly a pupil, involving complete third-nerve palsy. Differential In primar y care, only 25% of those with severe, thunderclap headache have SAH. A number of other pot entially devastating or treat- able conditions can present with thunderclap: intracerebral bleeds, cere- bral venous thrombosis, ischemic stroke, large artery dissection, colloid cys t of the third ventricle, SIH, RCVS. Although most cases will ultimately prove to be migrai ne or idiopathic, thunderclap headache should always be considered a neurological emergency . All patients deserve brain imaging, vascular imaging, and LP before ascribing the present ation to something innocuous. Sentinel headache SAH patients may earlier have experienced a sentinel headache, perhaps due to a small warning leak from the offending aneurysm ( 6%), but the picture is clouded by recall bias. As corrective surgery is more successful in the least symptomatic patients, be suspicious of any sud- den headache, particularly if associa ted with neck or back pain. Tests CT (early) shows subarachnoid or ventricular blood (Figur e 10.6) but misses approximately 2% of small bleeds. Delay >1 wk progressively drops the se nsitivity of CT to 50%. If a CT scan is negative, then a LP should always be performed in s uspected cases of SAH to analyze the CSF for blood or blood breakdown products. Always send two tubes (the first and last) for cell counts to help differentiate traumatic taps from S AH. The CSF in SAH is uniformly bloody in the early stages of SAH, and the supernatant is s tained xanthochromic (yellow) after a few hours due to hemoglobin breakdown to bilirubin. T he diagnosis is easy (and outcome unfortunate) in a neurologically devastated patient; it i s the patient presenting with head- ache alone who may be misdiagnosed and who stands the m ost to lose. Vascular imaging is needed to establish the presence, number, location, size, and type of aneurysm (including anatomic suitability for clipping vs. coiling). Noninvasive MR and CT angiographic techniques have improved to the point where they are nearly as usef ul as the gold standard invasive four-vessel angiogram. Management Obtain a neurosurgical o pinion (immediately if \206\223 level of consciousness, progressive focal deficit, or cere bellar hematoma sus- pected). Bed rest, BP control (maintain within normal range). Repeat C T if deteriorating. Re-examine CNS often. Prevent the need for straining with stool softene rs. Maintain euvolemia. Vasospasm due to the presence of irritating blood around the large vessels of the brain can lead to stroke. Treatment includes nimodipine, induced hypertensio n, hypervolemia, and y g o o r u e N l features Symptoms: Sudden (peaking within 365 hemodilution ( \200\234triple H therapy \200\235). In extreme cases, intra-arterial therapy may be required. Nimodipine (60 mg/4 h PO for 3 wks, or 1 mg/h IVI) is a Ca 2+ antagonist that improves outcome (give to all if BP allows). The defini- tive management of a cerebral aneurysm involves either surgical clipping of the aneurysm or intravascular coiling of the aneurysm lumen. The sooner the better, as rebleeding is a common mode of death in those wh o have had a subarachnoid hemorrhage. Rebleeding occurs in 30%, often in the first few days . Ultimate outcome is strongly correlated with the patient \200\231s neurologi- cal status on initial presentation. Many unruptured aneurysms are diagnosed incidentally on imaging st udies; management is discussed in Table 10.14. Table 10.13 Mortality in subarachnoid hemorrhage based on Hunt and Hess grading Grade I II III IV V Signs None Neck stiffness and cranial nerve palsies Drowsiness Drowsy with hemiplegia Prolo nged coma Mortality (%) 0 11 37 71 100 Almost all the mortality occurs in the first month. Of those who survive the first month, 9 0% survive a year or more. Table 10.14 Unruptured aneurysms The management of unruptured cerebral aneurysms is controversial, based on conflicting data series. In general, the risk of rupture is felt to be between 0.5 and 1.5% per year (thus, odds favor intervention in younger patients and expectant management in those with an othe rwise short life expectancy). There is some data to suggest that irregularly shaped, larger , and posterior circulation aneurysms have higher rupture rates. Careful consultation with a neurosurgeon and interventional neurora- diologist is warranted whenever unruptured aneur ysms are discovered, even incidentally. 366 y g o o r u e N Figure 10.6 l Blood from a ruptured aneurysm occupies the interhemispheric fissure ( top arrow ), a cresc entic intracerebral area presumably near the aneu- rysm ( next arrow down ), the basal cist erns ( third arrow down, right of midline ), the lateral ventricles (temporal horns, the tw o lateralmost arrows ), and the fourth ventricle ( bottom arrow ). CT images can be manipul ated to show only high-density structures such as bones and arteries containing contrast. H ere is a middle cerebral artery aneurysm. We thank Professor Peter Scally for these CT images and the commentaries on them. Intracranial venous thrombosis Isolated sagittal sinus thrombosis (47% of patients) Present ation: Headache, vomiting, seizures, papilledema (one cause of intracranial hyper- tension and is in the differential diagnosis of pseudotumor cerebri/IIH). If venous infarction or b leeding supervenes, focal neurologic deficit will be seen (e.g., hemiplegia). Sagittal sinu s thrombosis is usually accompanied by thrombosis of other sinuses; e.g., lateral (transver se) sinus thrombosis (35%, with VI and VII cranial nerve palsies, field defect, ear pain), cavernous sinus thrombosis (see below), sigmoid sinus thrombosis (cerebellar signs, lower c ranial nerve palsies), inferior petrosal sinus (V and VI cranial nerve palsies \200\224 Gra denigo \200\231s syndrome). Cortical vein thrombosis This may cause venous infarcts ( foc al signs), encephalopathy, seizures, and headache (including thunderclap). It usually occur s with concurrent sinus thrombosis, but may be an isolated event. Venous angiomas \200\224o therwise benign, dilated vascular structures \200\224may be predisposed to thrombosis. Pred isposing factors In 30%, no cause is found. Hypercoagulable states, genetic and acquired, s uch as pregnancy and the postpartum period, are risks factors for cerebral vein thrombosis (Table 10.15). Differential diagnosis (See subarachnoid differential diagnosis list) Pseudo tumor cerebri/IIH, RCVS. 367 Table 10.15 Hypercoagulable states predisposing to cere- bral vein thrombosis Systemic Conditions : Dehydration, diabetes, neoplasms, heart failure, renal disease, infla mmatory conditions (Crohn \200\231s, ulcerative colitis, rheu- matological disorders, Beh et \200\231s), pregnancy/postpartum Infections : Meningitis, cerebral abscess, septicemia , fungal infections, severe sinusitis Drugs : Oral contraceptives, androgens, antifibrinoly tics Hematological : Activated protein C resistance (factor V Leiden), protein C or S defic iency (rare), prothrombin gene mutation (G20210A), hyperhomocysteinemia (e.g., from MTHFR m utation), antiphospholipid antibodies Post-craniotomy Evaluation Cerebral venous thrombosis is commonly missed at initial presentation, as the in itial \200\234dry \200\235 noncontrast head CT often appears normal, and the signs can be subtle on a routine noncontrast MRI (without MRV) as well. Check that there are no signs of meningitis. Do an emergency MRI or CT scan. If CT is normal, proceed to LP, measuring the opening CSF pressure. If high, and the headache is persisting, but no subarachnoid bleed, s uspect cerebral vein thrombosis especially if presentation is acute or there are predisposi ng factors. Get further imaging. A contrast CT may show the \200\234empty delta \200\235 s ign, in which a transversely cut sinus shows a contrast filling defect (dark) in its triang ular cross section. Although angiography is the gold standard, MRV (best with contrast) and CTV (reconstruction of a carefully timed contrast CT) are being utilized as noninvasive sc reening tools with consid- erable success. Management Although there is a paucity of random ized trial data on the treatment of intracerebral venous thrombosis, the standard of care i s to anticoagulate with heparin, even in the setting of intracerebral hemorrhage . Manage \206\221 ICP and seizures as indicated. Catheter-based interventional radiographic procedur es may be successful in individual cases, but are not widely available or well studied. Cav ernous sinus thrombosis is a potentially grave condition typically resulting from the exten sion of nearby bacterial infection (e.g., meningitis, sinusitis, dental, orbital cellulitis ). It may present with cranial neuropathies (facial sensory disturbance and diplopia are co mmon; III, IV, V1, V2, VI, and sympathetics may be affected), chemosis (swollen conjunctiva ), exophthal- mos, and often obtundation. Dedicated imaging studies are diagnostic and, eve n with immediate antibiotic treatment, this septic thrombophlebitis is often fatal. Jugular vein thrombosis may occur as the result of central line placement, especially in criticall y ill patients or in the setting of other hypercoagulable issues. It may result in elevated ICP and may propagate intracranially. Septic jugular vein thrombosis (Lemierre \200\231s) may occur as the result of oral or pharyngeal infections, including peritonsillar pathology . Branch or central retinal vein occlusion presents with visual loss and dramatically abnor mal retinal exam, often with hemorrhage. Macular edema, ischemia, and complications due to neovascularization may result. 368