10.1.1 Cranial Nerves

MRS	Name of cranial nerve	Numbering of cranial nerve	Function	Features of cranial nerve lesion
Oh	Olfactory	1	Sense of smell	Anosmia
Oh	Optic	2	Vision	Vision loss
Oh	Oculomotor	3	Supplies all muscles of eye, except superior-oblique and lateral rectus Also supplies parasympathetic innervation of eye (pupillary constriction and lens accommodation)	Double vision + ptosis+ eye is down and out. (This is due to unopposed actions of fourth and sixth CN)b
To	Trochlear	4	Supplies superior-oblique muscle of eye (which moves eye down and out)	Double vision + eye is “up and in” (opposite of 3rd cranial nerve palsy)
Try	Trigeminal	5	Sensation of face (including cornea)	Loss of sensation in face, and increased risk of corneal injury
And	Abducens	6	Lateral rectus muscle of eye	Double vision + eye is deviated inwarda
Feel	Facial	7	Controls motor function of facial muscles	Ptosis, facial droop, and hyperacusis (facial nerve controls middle ear bones that help dampen loud sounds)
Very	Vestibulocochlear nerve	8	Hearing and balance	Tinnitus, hearing loss, and vertigo
Good	Glossopharyngeal	9	Swallowing, speaking Afferent-sensory arm of gag reflex	Dysphagia, dysarthria, and absent gag reflex
Vibes	Vagus	10	Efferent-motor arm of gag reflex Also controls swallowing and upper GI function
Ah	Accessory	11	Movement of shoulder and neck	Weakness of shoulder and neck muscles
Heaven	Hypoglossal	12	Tongue movement	Tongue deviates to affected side
aIsolated cranial nerve VI palsy (abducens nerve) can be due to increased intracranial pressure, Wernicke’s encephalopathy, etc.
bSee table on next page.

10.1.2 Eponymous Pupillary Abnormalities

10.1.3 Upper Motor Neuron versus Lower Motor Neuron Lesion

	UMN lesion	LMN lesion
Etiology	Lesion occurring anywhere in the pathway of blue line in the picture above (e.g., stroke in internal capsule)	Lesion occurring anywhere in the pathway of red line in the picture above (e.g., lesion in the anterior horn of spinal cord)
Muscle tone	Initially muscle tone is flaccid, then spasticity develops slowly (may take weeks)	Flaccid
Deep tendon reflex	Just like muscle tone, it can be hypoactive in initial stages. In later stages, they are increased	Decreased (!)
Strength	↓ 1 Pronator drift test is a sensitive test for UMN lesion. Patients are asked to extend their hands with their palm up and close their eyes. If one hand slowly pronates (turns inside), then pronator drift is positive.	↓
Atrophy	Present (due to disuse atrophy)	Present (due to combination of disuse atrophy and loss of neurotrophic stimulation (denervation))
Associated signs	Babinski reflex Clonus	Babinski reflex is negative Fibrillation: these are small amplitudes of contraction which can be detected by EMG. The only place where fibrillation can be seen with naked eye is tongue Fasciculation: larger amplitudes of contractions seen by naked eye
NSIDx	CNS imaging (CT or MRI of brain or spine)	EMG and NCS
Facial nerve	Only lower half of the face is affected. Frowning, raising eyebrow, and eye closing remain intact	The whole half of the face is affected (LMN facial nerve palsy is known as Bell’s palsy. This diagnosis is made by physical exam onlya
aBell’s palsy
Etiology: Lyme disease, sarcoidosis, viral infection (herpes virus), etc.
Management: In idiopathic cases or when viral infection is suspected, NSIM is oral glucocorticoids, preferably initiated within 3 days of onset. If patient has severe involvement, empiric oral valacyclovir should also be given in conjunction with steroids (disfiguring asymmetry of face, with no forehead motion and incomplete closure of eye are severe features). Most common (MC) complication is corneal ulceration due to difficulty closing the eye. Taping the eye shut and using ocular lubricants can prevent this.
Abbreviations: CNS, central nervous system; CT, computed tomography; EMG, electromyography; LMN, lower motor neuron; MRI, magnetic resonance imaging; NCS, nerve conduction study; UMN, upper motor neuron.

Cerebellar Signs:

Cerebellum controls fine movement of our body. Cerebellar pathology may have the following clinical features:

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  Dysdiadochokinesia = inability to perform a series of rapidly alternating movements. Ask the patient to keep one hand over the other and rapidly move the upper hand in alternating supination/pronation.

  
  
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  Dysmetria = the patient overshoots when attempting to reach something.

  
  
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  Ataxia = tendency to fall to the side of the lesion and broad based ataxic gait.

  
  
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  Nystagmus +/- double vision.

  
  
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  Intention tremor (because of dysmetria).

  
  
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  Slurred speech (dysarthria).

  
  
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  Hypotonia.

  
  
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  Pendular knee reflex = persistent back and forth swinging of leg.

Patients who present with cerebellar signs, NSIDx is CNS imaging with CT or MRI scan.

10.2.1 Presentations of Transient Ischemic Attack

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  CCS: patient woke up with symptoms of difficulty speaking and weakness in his right leg that lasted for 3 hours. Patient is currently asymptomatic.

  
  
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  CCS: sudden painless loss of vision (like a “dark curtain” over one eye) followed by spontaneous recovery. Dx is amaurosis fugax, which is a form of TIA involving the retinal artery (branch of internal carotid artery).

10.2.2 Territorial Stroke, Involved Arteries and Corresponding Focal Neurological Deficit/s

Artery/area involved	Motor weakness	Sensory deficits	Associated cranial nerve involvement	Associated neurological deficit/s
Left MCA territory or left ICA territory	Right arm > right leg	Right arm > right leg	Right upper motor neuron facial palsy	Right homonymous hemianopia (it is contralateral) Dominant right lobe involvement = Broca’s and Wernicke’s aphasia	+/- Conjugate eye deviation to the side of the lesion For example, left-sided stroke has left deviation of eye
Right MCA territory or right ICA territory	Left arm > left leg	Left arm > left leg	Left upper motor neuron facial palsy	Left homonymous hemianopia (it is contralateral) Nondominant left lobe involvement = left hemineglect syndrome (one is neglecting the weaker side of the body)a Constructional apraxiaa
Left ACA territory	Right leg > right arm	Right leg > right arm	–	Incontinence (bladder involvement)
Right PCA territory stroke	–	–	–	Left homonymous hemianopia Note: PCA area infarct causes contralateral homonymous hemianopia without motor or sensory deficits
Pure motor stroke due to lacunar infarct in left penetrating thalamic branches in posterior limb (or sometimes genu) of left internal capsuleb	Right arm, leg	–	+ Right UMN facial palsy +/- dysarthria/ dysphagia	No visual loss and speech/praxis is normal (no involvement of other higher cortical functions)
Pure sensory stroke due to lacunar infarct in penetrating thalamic branches usually in the left thalamusb	–	Right arm, leg	–
Brain stem strokesc
Left paramedian branches of PCA Medial mid brain infarction (Weber’s syndrome)	Right arm, leg	–	Left CN III (3)	Right UMN facial palsy
Left paramedian branches of basilar artery Medial pons infarction			Left CN VI (lateral gaze paralysis) with diplopia	–
Left vertebral artery or spinal artery medial medulla infarction			Left CN XII (tongue deviates to left; to the side of the lesion)	–
Left AICA or left (superior cerebellar artery) infarction of lateral pons	–	Right spinothalamic tract involvement (pain and temperature sensation loss)	Left CN VII (lower motor neuron facial palsy)	Lateral brainstem lesions may have the following common features: Ipsilateral Horner’s syndrome (ptosis, miosis) Ipsilateral Vth nerve (trigeminal) nucleus involvement Ipsilateral VIII nerve involvement (vertigo, nystagmus, and vomiting) Ipsilateral limb cerebellar ataxia
Left PICA lateral medullary infarction (Wallenberg syndrome)			Left CN IX, X (dysphagia, hoarseness, absent gag reflex)
Left thalamus (thalamic pain syndrome)	–	Right-sided pain aggravated by light touch (allodynia or dysesthesia) and hemi-sensory loss. Thalamic pain syndrome can be very problematic		+/- Athetosis, hemiballismus
a Constructional apraxia and hemineglect syndrome: when patient is asked to draw shapes or clock, this is what he will draw:
bLacunar strokes in internal capsule
cTo better understand brain-stem strokes, please refer to “In a nutshell” box in next page before proceeding further down the table.
Abbreviations: ACA, anterior cerebral artery; AICA, anterior inferior cerebellar artery; ICA, internal carotid artery; MCA, middle cerebral artery; PCA, posterior cerebral artery; PICA, posterior-inferior cerebellar artery; UMN, upper motor neuron.

In a nutshell

Cortical versus brainstem lesions	Cortical lesions have unilateral defects Also look for defects in higher cortical functions (creating and understanding words, vision, reasoning, etc.)	Brainstem lesions have crossed deficits; i.e., contralateral motor or sensory deficit with ipsilateral cranial nerve involvement Absence of defects in higher cortical functions
Lateral versus medial brainstem lesions	Lesions in medial brainstem involve contralateral corticospinal tract (motor weakness)	Lesions in lateral brainstem involve contralateral spinothalamic tract (sensory loss)
To determine location of the brainstem lesion, look at the cranial nerve involved	Midbrain	3, 4
	Pons	6, 7	Note: both CN 5 and 8 can be involved in lateral lesion of pons and medulla
	Medulla	9, 10, 11, 12

10.2.3 Aphasia

10.2.4 Management of TIA and Stroke

Emergency management of patients with suspected stroke (sudden onset persistent focal neurological deficit)

Legend: NSIDx, next step in diagnosis; NSIM, next step in management; FND, focal neurological deficit; BP, blood pressure

If workup reveals cardioembolic source (e.g., EKG shows new-onset a-fib), start long-term anticoagulation such as warfarin, apixaban. This can be started 48 hours after symptom onset, if area of stroke is small. In patients with large stroke, wait 1 to 2 weeks before starting anticoagulation.

10.2.5 Diagnostic Evaluation of TIA/Ischemic Stroke

10.2.6 Cardioembolic TIA/Ischemic Stroke

Suspect cardioembolic source in the following situations:

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  Bilateral stroke.

  
  
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  Stroke involving multiple vascular territories.

  
  
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  Large middle cerebral artery stroke.

If transthoracic echocardiography (TTE), electrocardiography (EKG), and cardiac telemetry fail to reveal the source and cardioembolic mechanism is highly suspected, NSIM is transesophageal echocardiography (TEE). If intracardiac clot is discovered, start anticoagulation.

If no obvious source of stroke is identified, the following pathophysiology might account for the TIA/ischemic stroke

10.2.7 Carotid Artery Stenosis

Background: Atherosclerotic narrowing of carotid artery is known as carotid artery stenosis. It typically occurs in patients with multiple risk factors for ASCVD.

Presentation: It may be detected incidentally on clinical exam when carotid bruit is heard. It can also present with stroke or TIA. Some patients may have hx of pulsatile tinnitus.

Diagnosis: Imaging of neck arteries will show the atherosclerotic narrowing and the degree of stenosis.

Management

10.2.8 Long-Term Antiplatelet Therapy in Ischemic Stroke or TIA patients

Additional points:

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  For patients already on anticoagulation prior to stroke/TIA, determine the risk of hemorrhagic transformation. If small stroke, continue anticoagulation (no need for addition of antiplatelet agent). If large stroke, hold anticoagulation until deemed safe to start (usually 1-2 weeks later), and in the meantime bridge with aspirin.

  
  
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  Long-term DAPT isn’t recommended for stroke beyond 1-3 mos, even if the patient was on an antiplatelet agent prior to the current stroke.

Hypertension and Stroke

HTN can predispose to the following pathologies that can lead to stroke:

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  Generalized atherosclerotic disease leading to atheroembolic stroke.

  
  
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  Lipohyalinosis of small arterioles which predisposes to lacunar stroke. MCC of lacunar stroke is HTN.

  
  
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  Formation of Charcot-Bouchard aneurysm

  
  
  
  

  ⁶ Charcot–Bouchard aneurysms are tiny aneurysms in small penetrating blood vessels. They are a common cause of intracranial hemorrhage. Berry aneurysms occur in larger arteries.

  and its subsequent rupture leading to hemorrhagic stroke.
  
  
  
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  Formation of berry (saccular) aneurysms with subsequent rupture leading to subarachnoid hemorrhage.

10.2.9 Intracranial Bleeding (Hemorrhagic Cerebrovascular Accident)

Etiology:

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  MCC is HTN

  
  
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  Amyloid angiopathy

  
  
  
  

  ⁷

  
  
  
  
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  Vascular malformation

  
  
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  Coagulopathy and head trauma

  
  
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  Cocaine and alcohol abuse

Presentation: Sudden-onset focal neurological deficit (FND) along with the following features that point toward hemorrhagic stroke

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  Features of increased intracranial pressure (ICP): bradycardia, abducens nerve palsy (lateral rectus palsy), papilledema, etc.

  
  
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  Severe headache

  
  
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  Vomiting

  
  
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  Altered mental status

  
  
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  Loss of consciousness

10.2.10 Hypertension and Intracranial Bleeding

MC sites of hypertensive bleeding (given in order of frequency) and their clinical presentation:

1. Basal ganglia (putamen) and adjacent internal capsule	Contralateral sensory and motor FND It may have UMN facial palsy and oculomotor nerve gaze palsy	MRI scan showing left basal ganglia hemorrhage. Source: Nontraumatic Intracranial Hemorrhage. In: Mattle H, Mumenthaler M, Taub E. Fundamentals of Neurology: An Illustrated Guide. 2nd ed. Thieme; 2017.
2. Cerebellum	Patient can present with features of increased ICPa (e.g., sudden onset of headache, nausea/vomiting, vertigo, papilledema), along with cerebellar signs such as ataxia NSIM is immediate neurosurgical evaluation	CT scan shows cerebellar hemorrhage. Source: Nonhypertensive Intracerebral Hemorrhage. In: Bähr M, Frotscher M, ed. Duus’ Topical Diagnosis in Neurology: Anatomy, Physiology, Signs, Symptoms. 4th ed. Thieme; 2005.
3. Pons	May present initially with deep coma due to involvement of reticular activating system May present with locked-in syndrome: quadriplegic patient with intact eye movement (cranial nerve III in midbrain is not affected) b
a There is not much room in posterior fossa, so even small cerebellar bleeds can increase ICP.
b Other causes of locked-in syndrome include: Central pontine myelinolysis: due to rapid correction of hyponatremia. Cardioembolic occlusion of paramedian branches of basilar artery which supply the central pons. Brainstem tumor or infection.
Abbreviations: FND, focal neurological deficit; ICP, intracranial pressure; UMN, upper motor neuron.

General management of intracranial hemorrhage:

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  Reverse anticoagulation, if present.

  
  
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  If there is extension of blood into the ventricles with hydrocephalus, emergent neurosurgical evaluation for shunting is recommended.

  
  
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  For hemorrhagic stroke with elevated ICP leading to midline shift and worsening mental status, NSIM is stabilization with intubation, short-term hyperventilation and mannitol, followed by surgical evacuation.

  
  
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  IV nicardipine or labetalol is used to target blood pressure < 160/90 or mean arterial pressure (MAP) of 110 mmHg.

10.2.11 Complications of Stroke (Ischemic/Hemorrhagic)

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  Ischemic stroke can have hemorrhagic transformation: patient with large ischemic stroke is at higher risk.

  
  
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  Seizure (caution: new-onset seizure is a contraindication for tPA).

  
  
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  Aspiration pneumonia: all patients who present with stroke should have a bedside or formal swallow evaluation.

  
  
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  Immobility that increases risk of urinary tract infection (UTI) and venous thromboembolism.

10.2.12 Differential Diagnosis of Stroke

⁹ Most of these conditions occur in young patients (< 50 years of age) with no risk factors for ASCVD or HTN.

10.2.13 Subarachnoid Hemorrhage (SAH)

Etiology:

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  MCC is rupture of berry (saccular) aneurysm. Risk factors for formation of berry aneurysm are HTN, smoking, adult polycystic kidney disease, and collagen disorders such as Marfan’s and Ehlers-Danlos syndromes.

  
  
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  Other rare causes of SAH are arteriovenous malformation (AVM) and mycotic aneurysms.

Presentation:

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  Sudden onset of severe headache (“worst headache of my life,” “thunderclap headache”).

  
  
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  Patients can also present with loss of consciousness and other features of increased ICP (e.g., abducens nerve palsy).

  
  
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  Fundoscopy may reveal subhyaloid hemorrhage +/- papilledema.

  
  
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  Exam reveals signs of meningeal irritation, for example, stiff neck (nuchal rigidity). Blood in cerebrospinal fluid (CSF) irritates the meningeal membranes.

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  Other focal neurological findings may include the following:

  
  
  
  
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    Cranial nerve deficits: oculomotor palsy is common (posterior communicating artery aneurysm is anatomically near to oculomotor nerve). Eye will be down and out.

    
    
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    SAH can also present with any form of FND related to anterior, middle, or posterior cerebral artery territory. This might be due to arterial spasms, hypoperfusion, or intracerebral clot.

Diagnostic evaluation:

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  Best initial test/NSIDx is CT scan without IV contrast. Earliest place where blood is typically seen is in the Sylvian fissure.

  
  
  
  

  ¹⁰ The fine, dense lines in the Sylvain fissure (black arrows) correspond to blood in the subarachnoid space. A small amount of blood is also seen in the posterior horn of the left lateral ventricle(red arrow) The green arrows are choroid plexus calcifications commonly seen in adults.
  Source: Perfusion Disturbances of the Brain. In: Eastman G, Wald C, Crossin J. Getting Started in Clinical Radiology. From Image to Diagnosis. 1st ed. Thieme; 2005.

  
  
  
  
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  If CT scan is negative and if there is a high degree of suspicion for SAH, NSIDx is lumbar puncture which may show xanthochromia and increased RBCs. Lumber puncture is the most sensitive test for SAH.

  
  
  
  

  ¹¹ With every 500 to 1000 RBC that enters CSF, 1 WBC will enter CSF.

  
  

  For example,

  
  

  1. CSF reveals 100,000 RBCs and only 50–100 WBCs: This WBC count is related to hemorrhage itself and isn’t a sign of meningitis.

  
  

  2. CSF reveals 100,000 RBCs and 8,000 WBCs: There are more than expected WBCs for the number of RBCs. In this case, hemorrhage alone does not account for increased WBCs. The likely dx is infection with hemorrhage (e.g., herpes meningoencephalitis with hemorrhage).

  
  

  Note: Major differential dx for SAH is meningitis.

  
  
  
  
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  NSIM after dx, is magnetic resonance angiography (MRA) to locate aneurysms.

Management:

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  Most appropriate treatment is interventional coiling. It involves placing a platinum wire under radiological guidance to clog-up the aneurysm. This is preferred over neurosurgical clipping (which requires craniotomy).

  
  
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  To prevent vasospasm, give nimodipine or verapamil (vasoactive calcium channel blockers) in all SAH patients. The major cause of morbidity and mortality in SAH is vasospasm of major arteries. The blood in the subarachnoid space may cause irritation of the smooth muscles of the major arteries causing vasospasms. This can cause infarction/ischemia in the corresponding arterial territories, causing TIA or stroke. This is called delayed ischemic neurological deficit as it can occur 3 days to 1 week after SAH.

Complications:

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  Hydrocephalus: CSF outflows are not designed to drain out viscous and cellular blood. Therefore, blood components may clog up CSF outflow drains. If hydrocephalus develops, NSIM is ventriculoperitoneal shunting.

  
  
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  Seizures: patient will generally require antiepileptic drug prophylaxis.

Prevention of SAH: Consider surgery for incidentally discovered aneurysms >7–10 mm in size.

Major differential diagnosis of SAH:

Dural or cerebral venous thrombosis

Risk factors: same as venous thromboembolism (see Chapter 3, for further information)

Presentation: symptoms of severe headache, altered mental status, seizures, and/or FND. Fundoscopy may reveal papilledema.

Workup: magnetic resonance venography (MRV) will confirm dx.

Rx: anticoagulation.