Background (J Clin Epidemiol 1991;44:1147; NAMCS 2009, cdc.gov/nchs/ahcd)

17% of US adults have had a severe headache in the past 3 mo; ♀ > ♂ by 2:1, more common in younger adults, people living in poverty (CDC

NCHS 2012;10:256)

Lifetime prevalence of HA as high as 90–100%, w/ 78% tension, 16% migraine

Common complaint in primary care; accounts for >1% of all outpt visits in US

Classification: Primary headache: Syndromes not due to another cause: E.g., tension, migraine, cluster; Secondary headache: Syndromes due to systemic illness or structural neuro abnormalities; primary HA syndromes often chronic conditions, established in early adulthood; new HA “pattern” should raise suspicion for secondary cause

Evaluation

History: First, determine if HA is new or old: “Have you ever had a headache like this before?” “How long have you been having these headaches?” → helps guide Ddx

Temporal qualities: Speed of onset, duration, time to max intensity, frequency Location: Unilateral (if so, always on same side?), retro- orbital

Triggers/alleviating factors: Trauma, position change (worse w/ supine → suggestive of ↑ ICP), sleep disruptions, stress, posture, neck pain Assoc sx: Phono-or photophobia, aura, N/V, vertigo, eye pain or visual changes, other neuro sx, fevers, myalgias Medications: Including OTC analgesics & frequency of use (med overuse HA), opioids, nitrates, caffeine, tobacco, EtOH, prior HA therapies Other: PMHx (immunosuppression), FHx of HA

Exam: VS (fever, HTN); Neuro exam w/ emphasis on CNs incl fundoscopic exam, visual fields, EOM; assess for meningismus Imaging: If suspicion for intracranial process & outpt w/u, MRI w/ gad preferred; if concern for emergent intracranial process → ED referral for

 

CT & further evaluation

 

Indications for Imaging

•  New HA in pt age >50, or new persistent daily HA

•  Unexplained change in HA character/freq

•  New cluster-type HA/TAC (Arch Neurol 2007;64:25)

•  HA awakening pt from sleep

•  HA ↑ w/ Valsalva or exertion

•  Trigeminal neuralgia w/ CNV deficit or b/l neuralgia (Neurology 2008;71:1183)

•  Atypical/new migraine aura (other than visual)

•  New HA assoc w/ vomiting

•  Abnormal neuro exam unexplained by known dx

(BMJ 2010;341:c4113; JAMA 2006;296:1274; AAN US Headache Consortium 2000 guidelines, aan.com)

Red flags: (any of these should prompt ED referral) New focal neuro deficit: incl ↓ visual acuity, diplopia; “Thunderclap” HA: explosive onset, “worst HA of life” (SAH); Evidence of ↑ ICP: Papilledema, HA ↑ when supine, ⊕ N/V, CNVI palsy (mass, venous sinus thrombosis); Meningismus (SAH or meningitis), Altered mental status (meningitis/encephalitis), Immunosuppressed w/ fever (CNS infection)

Chronic Headache Management

Headache diary: To identify triggers, pattern, freq, assoc sx, & response to tx; sample at americanheadachesociety.org

Medication: PRN abortive med for all pts, initiate ppx if >1 debilitating HA/mo

Counseling: Avoid triggers when possible, caution: re: use of abortive tx >2–3×/wk, may → med overuse HA

Neurology referral: Complex migraine w/ known neuro deficits; HA w/ autonomic features (e.g., TACs) or chronic HA (>15 HA/mo)

Patient information: National headache foundation at www.headaches.org, under “My Headache”

MIGRAINE

 

Background (Lancet 2004;363:381; JAMA 2006;296:1274; Med Clin N Am 2009;93:245)

Epidemiology: ~15% of women, 6% of men; prevalence peaks age 30–39 y; vast majority (>90%) have onset prior to age 40; ⊕ FHx present in 80% of pts; HAs often interfere w/ work & QoL; most pts have 1–4 migraines/mo

Classification

Migraine without aura: 70–80% of cases; recurrent HA lasting 4–72 h with N/V or photo-/phonophobia & ≥2 of the following: Unilateral, throbbing, mod–severe intensity, aggravated by routine activity; may progress to include allodynia (pain w/nonpainful stimulus, e.g., brushing hair, wearing a hat)

Chronic migraine: Migraine present for ≥15 d/mo

Migraine with aura: 18% of cases; lasts <1 h, often at beginning of migraine; visual aura most common; scotomas w/ colored edges, “zigzag lines”); carries ↑ risk of stroke—2× ↑ RR for pts <45 y, 9× ↑ RR if smoker, 7× ↑ RR w/ OCPs: Estrogen-containing OCPs contraindicated; progestin-only OCPs ok

Complex migraine: P/w neuro deficits (weakness, numbness, aphasia); must r/o stroke prior to dx; multiple subtypes organized by sx (basilar, vestibular, retinal)

Evaluation

History: Features which ↑ suspicion of migraine dx include hx motion sickness, ice cream HA or “brain freeze,” jet-lag, hangover HA, esp after red wine

Triggers: 85% of pts can identify triggers (may require help of HA diary); most pts have multiple triggers (mean ~3), individual HA may be multifactorial

 

Migraine Triggers (Med Clin N Am 2009;93:245)
Classification	Examples
Environmental	Change in weather (50%), heat, ↑ humidity, ↑ altitude
Emotional	Stress (80%), letdown after stress, vacation
Schedule disruptions	Lack of sleep, oversleeping, fatigue, missed meal
Sensory	Bright lights, glare, strong perfumes, cigarette smoke
Alcohol	(50%) can be general or limited to 1 type (red wine most common)

 

 

Food	(45%) chocolate, cheese, citrus, fried foods, cured meats/fish
Hormonal	Menstrual (50% of women; sole trigger in 14% of women)
Other	Minor head trauma, NTG, exertion, dehydration

Abortive Treatment (NEJM 2010;363:63)

Counseling: Environment: Advise quiet, dark room if episode occurs, avoid motion, stay hydrated; Meds: Take abortive Rx ASAP for max efficacy; avoid using >2×/wk as can → overuse HA; plan to develop “toolbox” of different medications for different presentations (mild/early vs. severe vs. refractory) w/ pt

Triptans: 5-HT agonists

Mechanism: Thought to inhibit release of vasoactive peptides & ↓ signaling to thalamus Efficacy: 6-mg SC sumatriptan most effective w/in class; for oral triptans, no clear benefit between agents, although in meta-analysis, 100-mg sumatriptan ≥ frovatriptan > naratriptan (Cephalalgia 2002;22:633); no clear evidence that triptans are more effective than other abortive tx & generally more $$$; if 1 triptan ineffective in 2 attacks, switch to another triptan; may consider combination tx w/ NSAID

Administration: ↑↑ Efficacy if given at HA onset, typically ineffective if pt has progressed to allodynia; onset 20–60 min Formulation: PO most common, but nasal sprays, SC, PR, & disintegrating tabs also available Sample Rx: Sumatriptan 50–100 mg at 1st onset of HA; may repeat × 1 after 2 h (max 200 mg/24 h) or rizatriptan 5– 10 mg; may repeat × 1 after 2 h (max 30 mg/24 h) Side effects: Paresthesias, flushing, mild, brief neck or chest pressure/tightness (not thought to be 2/2 coronary ischemia); can → overuse HA Drug interactions: Do not use w/in 24 h of ergot derivatives; ↑ risk of serotonin syndrome w/ SSRI or SNRI use Contraindications: Complex migraine, known CAD/stroke; severe hepatic or renal disease, uncontrolled HTN, hx coronary vasospasm, avoid w/ elderly pts or ↑ CAD risk (✓ baseline ECG, consider further eval) (Headache 2000;40:599; Headache 2004;44 Suppl1:S31)

 

Selected Abortive Medications
Medication	Considerations	Adverse Effects

 

NSAIDs	1st-line for mild–mod HA, OTC	PUD, AKI, ↑ risk of med overuse HA
ASA/APAP/Caffeine	1st-line for mild–mod HA, OTC	ASA: bleeding, APAP: hepatotoxicity; All: ↑ risk of overuse HA
Compazine	Antiemetic properties	Antidopaminergic (i.e., restlessness, akathisia, dystonia), ↑ QTc
Metoclopramide	Antiemetic properties	Antidopaminergic (see above)
Magnesium	Adjunct for photophobia	Diarrhea

Opioids not recommended; ↑ risk of rebound & misuse potential; (Headache 2012;S1:3)

Prevention

Indications: Should be considered for pts w/ >1–2 episodes/wk or when less frequent but prolonged or debilitating; consider other potential indications for individual ppx agents

Oral contraceptive pills: Consider continuous monophasic low-dose OCPs in pts w/ menstrual trigger; however, contraindicated in pts w/ aura & can worsen sx or cause pt to develop aura → d/c Rx (BMJ

2009;339:b3914)

Herbal/alternative therapies: Some data for: (1) acupuncture for ↓ frequency, # days & intensity of migraine w/o aura (JAMA Intern Med 2017;177:508); (2) magnesium citrate for ↓ severity & frequency of migraine (600 mg/d; s/e GI upset, diarrhea; Pain Physician 2016;19:E97), (3) Coenzyme Q10 for ↓ migraine frequency (100 mg TID; no s/e); (4) Riboflavin (400 mg/d for >3 mo; no s/e); Butterbur may ↓ migraine but not recommended 2/2 concerns for hepatotoxicity; Feverfew unlikely to be better than placebo (Headache 2009;49:966)

Other: For refractory or chronic migraine, local nerve block w/ botulinum toxin can be performed by neurologist (Cephalalgia 2010;30:804)

 

Migraine: Preventive Medications
Medication	Additional Indications	Adverse Effects
Propranolol	HTN, varices/GIB ppx	Depression, fatigue, ↓ BP/HR, ED
Topiramate	Obesity, seizure d/o	Paresthesias, nausea, wt loss, memory/ cognitive Δ, renal stones, teratogenic

 

Valproic acid (VPA)	Seizure d/o, mood d/o	Wt gain, ↑ LFTs, ↓ PLTs, tremor, ↑   NH3, med interactions, teratogenic
TCAs	Depression (↓ dose for migraine)	Arrhythmia, dry mouth, constipation, sedation, ↓ s/e in nortriptyline vs. amitriptyline
Verapamil	HTN, AF	↓ BP/HR, dizziness, facial flushing
Gabapentin	Peripheral neuropathy	Dizziness, sedation, wt gain, edema, ↓ mood

(Adapted from Neurology 2012;78:1337)

TENSION HEADACHES

 

Definition: ≥2 of following features: Bilateral, tightening quality, no change w/ movement, mild–mod severity & no N/V (anorexia possible),

≤1 of photophobia or phonophobia

Epidemiology: The most prevalent headache disorder; may be seen in migraine pts

History: Onset typically over hours, does not require change in daily activity

Triggers: Sleep deprivation, dehydration, hunger; assoc w/ myofascial sensitivity of head

Counseling: Identify stressors, comorbid contributors (e.g., depression)

Abortive treatment: See table: NSAIDs, APAP, ASA, analgesics (but risk of med overuse HA); tx cervicalgia if present

Ppx treatment: See table: TCAs (nortriptyline), biofeedback (Continuum 2012;18:823); some data for trigger point injections w/ lidocaine in ↓ HA frequency and thus analgesic use (J Headache Pain 2013;14:44); no support for Botulinum toxin (JAMA 2012;307:1736)

MEDICATION OVERUSE (REBOUND) HEADACHES

 

Definition: Subtype of secondary headaches in pts w/ a primary

 

headache syndrome

Triggers: Use of ergots, opiates, triptans, or combined analgesics >10 days/month or plain analgesics >15 days/month

History: HA worse after starting meds & improves after cessation of meds

Treatment: Multiple approaches: consider short course corticosteroids, taper w/ ppx med on day 1, ppx med alone; most important is withdrawal of offending med; mod–severe cases may require neurology input (Continuum Neurol 2012;18:807)

OTHER HEADACHE SYNDROMES

 

Trigeminal autonomic cephalgias (TAC) (Continuum 2012;18:883; JNNP 2002;72:ii19): Characterized by autonomic sx (rhinorrhea, lacrimation, red/tearing eye, miosis/ptosis), typically unilateral, subtypes differentiated by time course

Cluster: Unilateral orbital/temporal pain, restless, worse w/ EtOH & nitro, 15 min–3 h attacks, typically clustered in bouts of ~7 d unless chronic variant; Tx: Oxygen, nasal/SC sumatriptan, nasal lidocaine; CCB (verapamil) for ppx Hemicrania continua: ♀>♂, stabbing pain, continuous ≥3 mo; Tx: Indomethacin Paroxysmal hemicrania: ♀>♂, 2–45 min attacks; Tx: Indomethacin Short- lasting unilateral neuralgiform headache with conjunctival injection & tearing (SUNCT): Incidence ♂>♀, prevalence ↑ >50 y; Definition: Stabbing orbital pain, 15 s–5 min, may occur many times/d, often ⊕ by cutaneous stimulation; Tx: Few proven tx; consider lamotrigine

Trigeminal neuralgia: Onset >40 y, sharp unilateral electric shock sensation lasting s, precipitated by touching face or chewing (see “Jaw & Facial Pain”)

Secondary headache: Can present similar to migraine or as a change in frequency/quality/intensity of pt’s typical HA syndrome

GCA: Age >50, ♀ > ♂; fever/constitutional sx, jaw claudication, vision loss (50%) assoc w/ PMR; requires prompt tx if suspected (see “Polymyalgia Rheumatica”) Pseudotumor cerebri (Idiopathic

 

intracranial HTN): ♀ > ♂, age 20–40s, assoc w/ obesity, meds (vit A derivates, tetracycline, OCPs); S/sx: Worse w/ supine position, blurred vision/grey spots, pulsatile tinnitus, e/o ↑ ICP (see Red Flags, above); → ED if new case suspected; Dx: MRI w/ gad & MRV (to r/o mass/VST), bland LP w/ opening pressure >25 cm; Tx: Wt loss, acetazolamide, CSF diversion (large-volume LPs, shunt) → refer to Neurology/Neuro-ophthalmology Other: ↑ ICP (CNS mass/edema, hydrocephalus), ↓ ICP (CSF leak, overshunting), vascular causes (stroke, aneurysm/AVM, venous sinus thrombosis), posttrauma (concussion, ICH), meningeal irritation (meningitis, SAH), posterior reversible encephalopathy syndrome (PRES), TMJ syndrome, glaucoma

 

Background (Emerg Med Clin North Am 1997;15:649; Continuum 2014;20:942)

Definition: “double vision”; the duplicated visual image of a single object (noncongruence of the 2 images may be horizontal, vertical, diagonal, or torsional)

Binocular diplopia (resolves if 1 eye closed): most common; due to misalignment of the visual axes, most likely due to cranial nerve pathology

Monocular diplopia (persists if 1 eye closed) can be thought of as a form of “blurred vision”–-due to intraocular cause (macular edema, corneal or lens pathology), or central cause (CNS visual pathways) Cranial nerves involved in eye movement:

CNIII (oculomotor): Innervates medial, sup & inf rectus, inf oblique, lev palpebrae superioris, pupil constrictors (parasympathetic); CNIV (trochlear): Innervates superior oblique; CNVI (abducens): Innervates lateral rectus

Etiology: CN palsies common cause; these can be idiopathic, ischemic, traumatic, compressive (↑ ICP, aneurysm), neuromuscular junction disorder (myasthenia gravis); can also be due to pathology of the extraocular muscles themselves (trauma, orbital mass, muscular atrophy); wide range of etiologies & severity means appropriate eval &

 

triage crucial

Evaluation (Principles of Neurology 2009:261)

History: Ask about onset, trauma, PMHx including DM, HTN, thyroid disease; obtain key features of diplopia hx to determine localization (below)

 

Key Historical Features to Localize Common Diplopia Complaints
Clinical Feature	Localization
Monocular (persists w/ 1 eye closed)	Ocular defect → refer to ophtho
Binocular (disappears w/ 1 eye closed)	Neuro defect → refer to neuro
Horizontal (side-to-side) images	CNIII or VI lesion
Vertical (above-&-below) images	CNIV lesion, skew deviation
Improves w/ head tilt	CNIV (if tilt toward unaffected side) or CNVI (if tilt toward affected side)
Sx worse w/ near focus (e.g., reading)	CNIII
Sx worse w/ distant focus	CNVI
Sx worse at end of day	Myasthenia gravis
HA, N/V, weakness, numbness, dyscoordination	Intracranial pathology
Pain with eye movement	Myopathy

Exam: Full eye & CN exam: Assess for proptosis (Graves disease), ptosis (CNIII, Horner’s syndrome), lid lag (hyperthyroidism); fundoscopic exam for papilledema, pupil asymmetries (dilated pupil w/ compressive CNIII lesion; spared/normal pupil w/ ischemic CN III lesion) & response to light (see “Vision Loss” & “Ophthalmic Evaluation”)

Alignment testing:

Corneal reflection: Shine light in pt’s eyes while pt looking straight ahead; assess position of light’s reflection in pt’s corneas— asymmetry suggests misalignment Cover–uncover test: Assess for corrective movements as pt refixates (misalignment) (youtube.com/watch?v=yyIA-dl49Lg) EOM testing: Track examiner’s finger in an “H” shape; check for dysconjugate gaze (& note any worsening of diplopia) in each quadrant

 

Figure 9-1. The muscles and innervation of extraocular movements (L eye)

 

 

 

If concern for myasthenia, perform repetitive strength testing (expect decremental response) & check sustained upgaze for fatigable ptosis or diplopia; check neck flexion (surrogate for diaphragmatic function) Red flags: Headache, N/V, anisocoria, impaired pupillary light response, ptosis, multiple CN palsies, other neuro deficits, eye pain

Etiologies (Principles of Neurology 2009:261)

Cranial nerve palsies: III, IV, and VI control extraocular movement

 

 

 

 

Cranial nerve III palsy: Horizontal or “diagonal” diplopia

Findings: Impaired eye “down & out” when pt looks straight ahead, diplopia most severe when pt looks superiorly & toward unaffected side (“up & in”); ptosis ± dilated pupil Etiology: Most frequently intracranial compression by aneurysm (posterior communicating artery) or tumor (painful, usually w/ dilated pupil/impaired light response, but can have nl pupil if only a partial palsy) (J Neurosurg 2006;105:228); can also be due to ischemia/infarction (typically seen in DM) which is typically pupil-sparing & painless, although can present w/ pain over eyebrow

Cranial nerve IV palsy: Vertical diplopia, relatively rare as isolated finding

Findings: Most severe when pt looks “down & in” (toward unaffected side); pt will naturally tilt head toward unaffected side to compensate (worsened by head tilt toward affected side) Etiology: Traumatic (majority of cases—can occur even w/ very mild trauma), postsurgical, idiopathic, ischemic (Neurology 1993;43:2439; Neurology 2009;72:e93)

 

Cranial nerve VI palsy: Horizontal diplopia; most common CN palsy (JNNP 2004;75:iv24)

Findings: Most severe w/ lateral gaze toward affected side “out” Etiology: Idiopathic, ischemic microvascular disease (typically in poorly controlled DM), traumatic, ↑ ICP (6th nerve is most

susceptible 2/2 long intracranial course)

Skew deviation: Vertical diplopia that does not fit the pattern of a CNIV palsy; diplopia often equal in all directions of gaze; 2/2 lesions above CN nucleus (brainstem, vestibular system, cerebellum) (Continuum

2009;15:150)

Other: Cavernous sinus syndrome (⊕ proptosis, eye pain), superior orbital fissure syndrome (⊕ eye pain, ptosis), orbital apex syndrome (visual loss + palsy), MG (diplopia common initial presentation, sx usually ↑ w/ reading, watching T.V. or at end of day & assoc w/ ptosis), Guillain–Barré syndrome (Miller Fisher variant: Diplopia, ataxia, areflexia), hyperthyroid (2/2 inflammation of EOM), Wernicke encephalopathy (⊕ nystagmus, gait disturbance)

Management

Isolated monocular diplopia → Ophthalmology w/in 24–48 h Isolated binocular diplopia → Neurology/Neuro-ophthalmology w/in 24–28 h

Binocular diplopia with red flags (above) → ED for Neurology eval/imaging

 

Background (Continuum 2012;18:1060; Principles of Neurology 2009:288)

Definition: Vertigo is the inappropriate sensation of self or environment moving

The term dizziness can be used to describe

• True vertigo
• Lightheadedness/presyncope (2/2 cerebral hypoperfusion)
• Disequilibrium (sense of imbalance, can accompany vertigo or be distinct)
• Symptoms assoc w/ anxiety disorders

 

Epidemiology: Vertigo lifetime prevalence 20–30%, accounts for 1.7% of US ambulatory visits (Otolaryngol Clin N Am 2012;45:925)

Vestibular system physiology: Angular acceleration detected by fluid movement in the 3 semicircular canals (1 in each axis; see figures below); linear acceleration detected by movement of otoliths in adjacent utricle & saccule; these impulses → vestibular nuclei in pons/upper medulla which are interconnected w/ the cerebellum, cerebral cortex, & CNs involved in eye movements (III, IV, VI) via the MLF pathway

 

Figure 9-2. Semicircular canal orientation (enlarged, R ear)

 

 

 

Classification: Etiologies divided into peripheral causes of vertigo (inner ear dysfunction: BPPV, Ménière’s, vestibular neuronopathy) and central causes (brainstem, cerebellum lesions)

Peripheral etiologies are more common and generally benign; some central lesions require emergent tx, so important to determine if peripheral or central cause

Evaluation (AFP 2005;71:1115)

General approach: First, establish pt is experiencing vertigo & not other cause of dizziness; next determine central or peripheral cause using history/PE

History:

Establish vertigo as cause of sx: Ask pt to describe dizziness; ask “Did you feel like the room was spinning, or did you feel like you

 

were going to pass out?” (if c/w presyncope, see “Syncope”)

Onset: Sudden onset suggests central cause or Ménière’s

Duration: Brief episodes (<1 min) suggest BPPV, long

Aggravating factors: Precipitated by changing head position (BPPV), motion (peripheral) Peripheral process assoc sx: HA, prominent N/V, assoc tinnitus

Nonvestibular process assoc sx: CP, palpitations

CNS sx: Diplopia, other neuro sx, gait instability, N/V (central) Other: Hx trauma (carotid dissection), stroke risk factors, medication list

Exam: VS (assess for orthostasis if ? of presyncope), otoscopic exam

Cranial nerves; complete exam, looking for nystagmus, diplopia, Horner’s Cerebellar exam: Assess for dysmetria, ataxia, wide- based gait, Romberg’s Hearing: Assess for sensorineural hearing loss w/ Weber & Rinne tests (see “Hearing Loss”)

Head impulse-nystagmus-test of skew (HINTS): 3-step exam; if all 3 findings suggest central cause → Se/Sp 100%/96% for stroke (Stroke 2009;40:3504); caution in pts w/ severe neck or vascular disease

Head-impulse test: Ask pt to focus on fixed object straight ahead, examiner turns pt’s head abruptly to each side (~30°): ⊕ test = when head turned toward affected side, eyes make a corrective saccade to redirect gaze to desired target → peripheral lesion Nystagmus: Assess for nystagmus in all directions; peripheral lesions classically have horizontal nystagmus worst when looking toward affected side (eccentric gaze) Skew deviation: Vertical ocular misalignment; indicates central (brainstem) locus; Look for vertical displacement of eye w/ alternating cover of each eye

 

Features of Central versus Peripheral Vertigo
	Peripheral	Central
Head-impulse test	⊕ Saccades	Absent (normal)
Nystagmus
Direction w/ head in fixed position Direction variability Effect of visual fixation Reversal of head position	Often horizontal, but can be mixed horizontal/rotational or vertical/rotational Unidirectional—never Δs direction	Pure horizontal, pure vertical, or pure torsional Δ direction w/ gaze No effect No effect

 

	Inhibits Can Δ direction of nystagmus
Skew	Absent	Present
Other	Pronounced nausea Deafness/tinnitus	Postural instability/falls Other neuro signs

Diagnostics: If suspect central etiology, ED eval for further w/u; no imaging for BPPV

Red flags: Neuro deficits, severe HA/nausea, ⊕ HINTS test, central

nystagmus or any concern for mass/structural lesion

Differential Diagnosis (NEJM 1998;339:680; Otolaryngol Clin N Am 2012;45:925)

Benign paroxysmal positional vertigo: Common, ♀ > ♂, ↑ w/ age

Etiology: Peripheral; dislodged otoliths in semicircular canals (90% posterior canal, tx w/ Epley, below) S/sx: Recurrent, transient & episodic last <1 min, can be triggered by specific head position Δs (lying on 1 side, turning over) (Semin Neuro 2009;29:500) Dix– Hallpike: Evaluates for posterior canal otolith; attempt on both sides; ⊕ test = nystagmus & vertigo, often after 2–5 s delay, w/ affected ear down → BPPV; however relatively ↓ Se (⊖ test doesn’t definitively r/o BPPV) (1) Examiner holds pt head, rotates 45° toward one side

• Tip pt backward to supine position w/ head overhanging edge of table, still rotated to the side (45°) Tx: Otolith repositioning maneuvers (Epley, Semont, Brandt–Daroff); caution: 36% of posted videos inaccurate (Neurology 2012;79:376)

 

 

 

Epley: Repositioning maneuver for posterior canal otolith; see AAN video at: youtube.com/watch?v=hq-IQWSrAtM; consists of Dix– Hallpike + 2 more steps (1, 2) Start w/ Dix–Hallpike to affected side & maintain for 1–2 min

• Turn head 90° to unaffected side, hold add’l 1–2 min
• Roll body to unaffected side so head facing obliquely downward

 

(add’l 90°), hold 1–2 min more (5) Keeping head toward unaffected side, slowly return to upright position (Pract Neurol 2008;8:211; Semin Neuro 2009;29:500)

Ménière disease: Age 20–40, 10–50% b/l, prevalence <0.1%

Etiology: Peripheral: 2/2 expansion of endolymphatic sacs in labrinyth; idiopathic or 2/2 trauma, infection S/sx: Recurrent vertigo

+ fluctuating deafness/tinnitus; sense of ear pressure; abrupt onset, attacks last min–h

Tx: Supportive (PT), meclizine, scopolamine, promethazine, mild sedative, salt restriction; for severe/refractory disease → chemical labyrinthectomy vs. surgery (Continuum 2012;18:1087)

Acute vestibular neuronopathy or “acute vestibular neuritis” (Neurol Clin

2012;30:61)

Etiology: Peripheral; presumed viral; can occur post-URI

S/sx: Persistent sx lasting days-weeks, typically worst in 1st d with gradual resolution; subacute onset, ⊕ head-impulse test Tx: Supportive (PT), no e/o improved sx w/ corticosteroids, full recovery can take weeks (Cochrane Database Syst Rev 2011;5:CD008607; Otol Neurotol 2010; 31:183)

Central causes:

Posterior circulation TIA/stroke: Assess for risk factors (age >60, HTN, HLD, DM, smoking, CHF, AF) & assoc sx; neck pain/trauma

→ suspect vertebral dissection: 20% of stroke cases in young pts, incidence 1/100,000 → ED

Posterior fossa mass: HA, gradual onset, other neuro sx (above) → ED

Meds/toxins: Barbiturates, benzos, EtOH, AEDs (incl gabapentin), hypnotics (Am Fam Med 2010;8:196) if no e/o brainstem lesion may consider close observation w/ removal of offending agent Vestibular migraine: ♀ > ♂, past hx migraine, nl exam, or may have central nystagmus → if suspect, refer to neurology

When to refer

If red flags (above), pt high risk for stroke & cannot r/o central process

→ refer to ED for urgent CT or MRI

Consider neuro referral if dx unclear or for difficult to control/persistent

 

sx, including BPPV unres ponsive to Epley; may also consider vestibular PT for BPPV & Ménière’s

 

Background (NEJM 2004;351:1323; AFP 2007;76:997; Otolaryngol Head Neck

2013;149:S1)

Definition: Bell’s palsy is an idiopathic unilateral acquired facial nerve palsy; some suggestion that this may be 2/2 HSV-1 (⊕ HSV DNA in affected CNs)

Physiology: CNVII innervates ipsilateral muscles of facial expression; also contains parasympathetic fibers → ⊕ lacrimal & salivary glands, provides some taste to anterior 2/3 of tongue

Epidemiology: 0.2–0.3% annual risk; incidence peaks in 40s, ↑ risk assoc w/ DM, HTN, pregnancy, HIV (CID 2007;44:e27)

Natural history: Most pts (71%) w/o tx fully recover (full recovery seen in 94% w/ partial palsy, 61% w/ full palsy); recurrence in 7–15%; Poor prognosis: Elderly, HTN, pregnancy, complete paralysis, pain other than in ear, severe pain, ↓ taste; Good prognosis: Partial paralysis, early (1st wk) recovery of motor function, recovery of taste before motor function

Evaluation (NEJM 2004;351:1324; Otolaryngol Head Neck 2013;149:S1)

General approach: Obtain complete hx & perform full HEENT & neuro exam on all pts; clinical diagnosis based on classic findings; pts w/ atypical features require further testing; those w/ red flags require emergent eval

 

Classic Presentation Bell’s Palsy
History	Sudden onset; rapid evolution to max facial weakness w/in 48 h; ipsilateral hyperacusis (2/2 paralysis of stapedius muscle), ear pain or fullness, ± retroauricular pain preceding weakness, ± ↓ lacrimation, salivation, & taste (anterior 2/3 of tongue); fullness of face (but no sensory loss)
Exam	Partial or complete ipsilateral paralysis of CNVII, including forehead, is only expected finding; assess eyebrow elevation, eye closure, nasolabial fold,

 

cheek puff, lip purse, taste & platysma muscle; may include ↓ lacrimation, salivation, or taste depending on segment affected

 

 

 

 

 

 

 

Features suggestive of alternative diagnosis (BMJ 2004;329:553)

Hx: Gradual onset (suggests compression, e.g., neoplasm), headache, loss of sensation or add’l neuro sx (CNS lesion), trauma (mechanical injury or CNS lesion), hearing loss, vertigo (CPA lesion, Ramsay Hunt), recurrent

Exam: Bilateral disease (e.g., Lyme, HIV, sarcoid, GBS), palpable mass (peripheral compression, e.g., parotid tumor), otoscopic abnormalities (cholesteatoma, vesicles of Ramsay Hunt), oral lesions (VZV vesicles, tonsillar asymmetry suggestive of tumors), rash (Lyme), other CN/neuro abnormalities

Differential diagnosis:

CNS lesions (stroke, neoplasm, demyelination, CPA mass):

Pons/CNVII nucleus: ⊕ Brainstem signs like contralateral body

 

hemiparesis, sensory loss, ataxia, nystagmus, abnl eye movements Cerebral/supranuclear: Forehead spared, salivation & taste intact despite ↓ lacrimation; arm/leg weakness Peripheral lesions: Ramsay Hunt syndrome (VZV reactivation in CNVII; can occur as pain w/o vesicles, i.e., zoster sine herpete), Lyme, Guillain–Barré (often b/l), head & neck tumor, ear lesion (otitis media, cholesteatoma), sarcoid, Sjögren’s

Labs: None indicated if classic hx/PE, consider Lyme testing if ↑ clinical suspicion or high-risk pt in endemic area (see “Tick-Borne Illness”), consider HIV testing

Imaging: Typically none indicated; if gradual onset, suspicious HA but no suggestion of acute central process requiring ED referral → neuroimaging; LP if suspect neuro Lyme

Other: Nerve conduction studies (NCS) may be useful for prognosis in complete paralysis, but not routinely recommended; not recommended in incomplete paralysis

Treatment (Neurology 2012;79:2209; NEJM 2007;357:1598)

Corticosteroids: 40–60 mg prednisone QD × 7 d, started ASAP, ideally within 48 h of sx onset (prompt tx → 40% ↑ RR of complete recovery of motor function at 6 mo vs. placebo; NNT 6–8) (Cochrane

Database System Rev 2016:CD001942)

Other: Antivirals (for presumed HSV) not shown to be effective in most RCTs (NEJM 2007; 357:1598) but ? of small benefit & may be offered; valacyclovir & famciclovir preferred 2/2 ↑ adherence; PT not shown to be beneficial or harmful; evidence lacking for acupuncture (BMJ

2009;339:b3354; Cochrane Database System Rev 2012:CD006283 & 2010:CD002914)

Early complications: Incomplete eye closure can → corneal abrasion; artificial tears q1h; eye ointment; eye patch at night, ophtho referral if any sx

When to refer: New or worsening neurologic findings → neurology/ENT, development of ocular symptoms → ophtho; incomplete facial recovery 3 mo after initial sx onset → neurology/ENT Late complications: Synkinesis (voluntary movement of one muscle

→ involuntary movement of another, e.g., winking → mouth twitching) & facial spasms can be treated w/ botulinum toxin

When to refer: If suspect CNS lesion → ED; Ramsay Hunt → ENT;

 

atypical presentation → Neurology; no improvement in 6-12 weeks or late complications → Plastic Surgery

 

Background

Definition: Clinical diagnosis defined (DSM-5) by e/o significant cognitive decline in ≥1 cognitive domain (learning & memory, language, executive function, complex attention, perceptual-motor, social cognition) & ADL/IADL difficulties

Mild cognitive impairment: Cognitive or memory problem worse than nl aging, but w/ preserved function so not meeting dementia definition (JAMA 2007;297:2391; 2008;300:1566; NEJM 2011;364:2227); progression to

dementia ~6–25%/y

Epidemiology: Incidence ↓ in high-income countries, perhaps 2/2 ↑ educational. attainment in older adults (JAMA Intern Med 2017;177:51), yet

~5.5M pts in US in 2017, expected to triple by 2050; costly ($259 billion/y) & burdensome (caregiver stress), affects 30% of >65 y Risk factors:

Definite: Age (strongest RF for all dementia); CV risk factors (HTN, DM, HLD), hx stroke, FHx, hx head trauma, hx delirium (8x ↑ in incident dementia + accelerated decline in cognition, Brain 2012;135:2809), hx SUD, Down syndrome (<1% for early AD, ~50% for FTD) Possible: Fewer years of formal education (JAMA Intern Med 2017;177:51) Protective: No strong data beyond lifestyle modification; unclear evidence for intellectual/social activity, exercise, antioxidants (e.g., Curcumin), statins, ω-3 fatty acids, Mediterranean diet, Ginkgo biloba (JAMA 2008;300:2253)

Ddx: Important to r/o potentially reversible causes of cognitive impairment: Chronic SDH, delirium, depression, NPH, hypothyroidism, malignancy (systemic vs. brain tumor), meds, infections (neurosyphilis, encephalitis, meningitis, Lyme), electrolyte imbalances and toxic metabolic etiologies, vit B1₂, folate or thiamine deficiency, heavy metal

poisoning

 

Dementia Subtypes
Type	Symptoms
Alzheimer (AD) (50–80%) (Lancet 2011;377:1019)	Memory deficit prominent; language, visual–spatial disturbances, indifference, neuropsych sx; parkinsonian sx = late manifestation; often anognosomic (unaware of deficits)
Vascular (VD) (10–20%) (Lancet Neurol 2003;2:89)	Abrupt onset, stepwise deterioration, fluctuating course, executive dysfunction may be prominent, hx stroke/stroke risk factors, focal neuro s/sx
Mixed (50% of AD) (JAMA 2004;292:2901)	Abnormalities characteristic of >1 dementia syndrome simultaneously (most commonly AD & VD together)
Lewy body (5–10%) (LBD) (AFP 2006;73:1223)	Dementia onset concurrent w/onset of parkinsonian sx (in PD dementia onset >1 y after motor sx); visual hallucinations, delusions, fluctuating cognition, sleep d/o, autonomic dysfunction (falls, orthostasis)
Frontotemporal (FTD) (12–25%) (AFP 2010;82:1372)	Personality/social/language/behavior problems prominent early sx, incl disinhibition; memory less affected; onset late 50s–early 60s; often anognosomic
Parkinson (see “PD”) (Lancet Neurol 2012;11:697)	Cognitive decline >1–2 y after onset of motor sx; executive & visual–spatial sx are prominent early
Other:	EtOH, Creutzfeldt–Jakob disease, cerebral amyloid angiopathy, HIV-associated dementia

Evaluation and Prognosis (AFP 2005;71:1745; 2011;84:895; JAMA 2007;297:2391)

Screening: USPSTF—insufficient evidence for/against routine screening

History: Important to talk to family members/caregivers about changes from baseline and difficulties w/ ADLs (grooming, managing finances, difficulty w/ learning/memory/language, driving, getting lost); timeline/progression (to distinguish from delirium); meds; r/o depression (“pseudodementia”); assess pt insight on deficits

Exam: Neuro exam, including gait/balance, (see “Falls”) cogwheel rigidity, tremors

Screening tests: Montreal cognitive assessment (MoCA) and MMSE are brief screening tests for various domains of cognitive impairment (BMC Geriatrics 2015;15:107) and can help monitor disease progression over time; less sensitive (more false ⊖) in pts w/ ↑ baseline cog function; consider formal neuropsych testing if no clear deficit captured on MoCA or MMSE but persistent sx;

 

consider language barriers when testing as can ↓ score

Workup: Dx primarily clinical; focus of labs/imaging is to r/o reversible causes: CBC, CMP, B1₂, TFTs, ± RPR (based on suspicion)

Brain imaging: Not always required if confident of clinical dx/will not change mgmt, but can be useful to exclude structural etiologies at initial eval, identify dementia subtype based on atrophy pattern Neuropsychological testing: If available, can quantify domain & degree of impairment (AFP 2010;82:495); may guide safety eval; best if family/friend can also attend

Prognosis: Highly variable as diagnosed at different stages; etiology- and age-based, dependent on comorbidities; pts w/ advanced dementia in nursing homes typically die of PNA, fevers, eating problems (NEJM 2009;361:1529); hospice/palliative care involvement helpful (JAMA 2007;298:2527) esp early, to help pt & family define GOC

Treatment (AFP 2006;73:647; 2011;83:1403; NEJM 2010;362:2194)

Supportive care: Exercise (JAMA 2003;290:2015; 2008;300:1027), occupational training, caregiver training & support, EtOH abstinence/moderation; minimize pain; treat depression, which may manifest as agitation; sleep hygiene; monitor for medical illness (i.e., UTI, PNA) & med toxicity; identify triggers for behavioral problems Medication toxicity: underappreciated source of ↓ cognitive function; avoid deliriogenic (BZDs, opioids), anticholinergic (antihistamines, TCAs, antipsychotics) (BMJ 2006;332:455)

Medications: Currently no tx reverse or stop disease progression; some evidence that cholinesterase inhibitors and memantine can slow pace of decline Cholinesterase inhibitors (CI): Donepezil ≈ galantamine

≈ rivastigmine in mild–mod AD (MMSE 10–26); consider combination of galantamine & donepezil in severe AD (MMSE<10); after 8–12 wk trial of tx, reassess clinical status & continue if improvement noted; restart if clinical deterioration after d/c; may help w/ neuropsychiatric sx in AD (JAMA 2003;289:210)

 

Pharmacotherapy of Dementia
Drug & Dose	Side-effects/Comments
Donepezil 5 mg PO QD × 4 wk → 10 mg QD	CI; benefit in severe AD alone (Lancet 2006;367:1057) & w/ memantine (NEJM 2012;366:893) & in LBD (Ann Neurol 2012;72:41); well tolerated due to ↓ peripheral anticholinergic activity;

 

	transient diarrhea, nausea; rare sx bradycardia
Galantamine 4 mg PO BID × 4 wk, up titrate qmo to 12 mg BID; ED available	CI; benefit reported in severe AD (Lancet Neurol 2009;8:39) & VD (Lancet 2002;359:1283); cognitive benefits sustained for >3 y in AD (Arch Neurol 2004;61:252); ↑ nausea, anorexia, wt loss compared to donepezil; take w/ food
Rivastigmine 1.5 mg PO BID, uptitrate q2wk to 6 mg BID; Transdermal available	CI; efficacious in PD dementia (NEJM 2004;351:2509), LBD (Lancet 2000;356:2031); ↑ severe nausea, anorexia c/w donepezil; HA; take w/ food; may worsen tremor in PD; significantly less GI s/e w/ transdermal patch; patch may cause rash
Memantine 5 mg PO QD → 5 mg BID → 5/10 → 10 BID in qwk increments	Neuroprotective NMDA antagonist; beneficial alone & in combination w/ donepezil in mod–severe AD (JAMA 2004;291:317; NEJM 2003;348:1333); s/e include dizziness, hallucinations & confusion (rare)

Antipsychotics: Both typical & atypical antipsychotics ↑ risk of death (NEJM 2005;353:2335); frank discussion of risks/benefits w/ caregivers & shared decision-makingre: possible Rx; preferable to dx/address underlying etiology of agitation whenever possible; if behavioral sx cannot be managed by other means, reassessment & documentation necessary (JAMA 2005;294:1963)

Typical antipsychotics: No benefit in improving neuropsych sx (JAMA 2005;293:596); Atypical antipsychotics: When compared w/ placebo for pts w/AD and psychosis, no significant benefit but significantly more s/e (NEJM 2006;355:1525)

Nutrition: Most advanced dementia pts will experience eating problems and weight loss in final stages; tube feeding not recommended (J Am Geriatr Soc 2014;62:1590); no evidence of benefit (Cochrane Database Syst Rev 2009;2:CD007209)

Mood stabilizers: Conflicting data to support use (e.g., valproic acid, (ox)carbamazepine, gabapentin, topiramate, lamotrigine); unclear benefit w/ potential for SES; consider psych/neuro c/s before initiating, discuss risks/benefits w/ pt’s surrogate decision maker

Driving: Clinical Dementia Rating (CDR) can be useful in assessing driving safety (Neurology 1993;43:2412); pts w/ CDR ≥2 are unsafe to drive; pts w/ CDR 0.5–1 should be evaluated for driving ability if risk factors present: (1) hx motor vehicle accidents or tickets; (2) MMSE ≤24; (3) caregiver concerns; (4) aggressive/impulsive behavior; (5) driving <60 miles/wk; (6) situational avoidance; (7) EtOH use, meds that affect CNS, sleep d/o, hx falls, or hearing/visual/mobility impairment (Neurology

 

2010;74:1316); pts may be referred for road-test driving assessment; document that recommendations conferred to family/pt/caregiver; mandatory reporting of unsafe drivers varies by state

Home safety evaluation: (PT, OT) Work with caregivers and families to assess need for placement in a more supervised setting; may ↓ mortality (JAGS 2006;54:950)

Wandering: Alzheimer’s organization offers (for $55, then $35/y) bracelets/jewelry/wallet card identification for dementia pts at ↑ risk of becoming lost

Money: Durable financial power of attorney, joint accounts, living trust (JAMA 2011;305:698)

Advance care planning: Start early; involve pt as much as able; see

“Advance Care Planning”

Patient information: MCI (JAMA 2009;302:452); dementia (AFP 2010;304:1972); Alzheimer’s: alz.org; theaftd.org, AFP 2011;83:1415; FTD (AFP 2010;82:1378); behavioral problems (AFP 2006;73:653); caregiver support (AFP 2000;62:2621); driving w/ dementia (AFP 2006;73:1035); finances (AFP 2011;305:1610)

 

Background (AFP 2012;85:123; Neurology 2013;80:2250)

Definition: Trauma-induced head injury with transient AMS (± LOC); consider mild TBI w/ functional impairment (no structural correlate on neuroimaging)

Natural history: Symptoms typically resolve spontaneously w/in 3–7 d (J Neurotrauma 2009;26:2365); during this time pts may be at ↑ risk of brain injury w/ even mild head trauma (“Second Impact Syndrome”) (Clin Sports Med 1998;17:37); in some cases recovery is more prolonged Epidemiology: 1.6–3.8 million sports concussions annually (J Head Trauma Rehabil 2006;21:375); elderly also at ↑ risk (see “Fall Prevention”)

Evaluation (NEJM 2007;356:166; AFP 2012;85:123; Neurology 2013;80:2250)

History: Obtain detailed history of mechanism of injury; any anticoagulation use; most common acute sx are HA (87%), dizziness (65%), & confusion (57%); can also present w/ postural instability,

 

amnesia (typically of the event and immediately before and/or after), incoherent speech, diplopia, seizures, drowsiness, nausea, photo-

/phonophobia, anxiety, irritability; LOC in only 10%; may be assoc w/ convulsions immediately after injury (J Neurotrauma 2009;26:2365) Postconcussive symptoms: HA, dizziness, & difficulty concentrating, cognitive deficits; can last days-weeks, occasionally months; no evidence that a single concussion → permanent neuro impairment; research ongoing on effects of multiple head injuries on cognitive function (JNNP 2010;81:1116); ↑ risk of seizures w/in 5 y from event (80% within 2 y); Risk factors for postconcussive sx: low socioeconomic status, previous TBI, coexisting injury, ongoing court case, ♀ > ♂ (Neurology 1995;45(7):1253), h/o depression/anxiety

Physical: Neuro exam, focusing on attention, memory, balance; C- spine eval; consider assessment tools such as the Standardized Assessment of Concussion (most commonly used for athletes: concussioncorps.org/wp-content/uploads/2013/04/SAC.pdf)

Red flags: Any focal neuro deficits, coagulopathy, e/o basilar skull fracture (hemotympanum, raccoon eyes, Battle sign), vomiting, dangerous mechanism of injury, persistent AMS (GCS <15), clinical deterioration → ED

Imaging: Normal in concussion; consider noncontrast head CT to r/o more serious TBI if: age ≥65, coagulopathy, vomiting, severe HA; the other indications for imaging are red flags (above) which should → ED evaluation; if neuroimaging indicated and cannot be obtained urgently (same-day) as an outpatient with proper f/u → ED (Ann Emergency Med 2008;52:713; Neurology 2013;80(24):2250)

Treatment (J Clin Neuroscience 2009;16:755)

Reassurance and education: Indicated for all pts → ↓ incidence + duration of postconcussive sx; counsel pts to f/u by phone or visit until sx resolved (AFP 2012;85:123)

Return to work/school/activities: Variety of approaches, emphasis on:

(1) Brief period of physical/cognitive rest; counsel pts that sx might initially persist (2) Graded stepwise return to cognitive/physical activities as tolerated; if sx return, fall back to lower level of activity

(3) Athletes: may not return to play while sx (↑ risk of re-injury w/ ↑

 

sequelae)

Symptom management: See table

 

Postconcussive Symptom Management
Symptom	Recommended Management
Dizziness/nausea	Meclizine & antiemetics
Headache	Mild PRN analgesics; if prolonged → standard migraine tx (see “Headache”)
Seizures	No need for AEDs unless seizures persist/recur
Cognitive dysfunction	Consider cognitive eval/OT/SLP referrals, depending on occupation
Anxiety, posttraumatic symptoms, impaired coping, persistent sx	Cognitive behavioral therapy

When to refer: If sx persist >1–2 wk, including HA not responsive to 1st-line agents or persistent cognitive complaints, seizures → Neurology

Patient information:

cdc.gov/traumaticbraininjury/pdf/tbi_patient_instructions-a.pdf

 

Background

Definition: A loss of muscle power and may be due to injury to the brain, spinal cord, nerve roots, peripheral nerves, neuromuscular junction, or muscle; however, the term “weakness” is often used nonspecifically by the patient & can be used to describe fatigue, pain, joint dysfunction/injury, psychosomatic or “functional” weakness Appropriate evaluation of muscle strength is important to determine if true weakness is present & help determine etiology; “weakness” may be presenting complaint for wide range of diseases (e.g., acute illness, depression, anemia, OA); so precise hx/PE important

Evaluation (Continuum 2011;17:1040; AFP 2005;71:1327)

History:

Onset: Acute (vascular), subacute (meds, rheumatologic, infectious),

 

or chronic (metabolic) Precipitants: Stress (functional), trauma, fever/infection

Distribution (localizes deficit): Focal, segmental, unilateral, or diffuse?

Symmetric? Proximal, distal?

PMHx: DM, CKD, HIV, cancer, recent critical illness, FHx

Meds/toxins: Statins, fibrates, corticosteroids, colchicine, chloroquine, EtOH, cocaine Assoc sx: Incontinence/retention of stool or urine (spinal cord process), diplopia (myasthenia), slurred speech, sensory sx, HAs (complex migraines, stroke/ICH)

Red flags: Acute onset, rapid progression, SOB (esp w/ sitting up) or resp involvement, bulbar sx (difficulty speaking, chewing, swallowing); urinary retention → ED referral

Exam: Investigate any other systemic sx as directed by hx; examine for muscle atrophy & tone, assess symmetry; eval muscle strength, clonus, DTRs, sensory exam (✓ for sensory level if concern for cord lesion) Muscle strength assessment: Verbally encourage pt to offer maximum effort for 1–2 seconds “Push hard, hard!”

 

Grading of Muscle Strength
0	No muscle contraction
1	Muscle contraction without movement at joint
2	Limb/joint movement but ⊖ antigravity strength
3	Able to maintain strength against gravity but unable to resist
4	Able to resist temporarily, but cannot sustain/power ↓
5	Normal power against resistance

Upper (UMN) vs. lower motor neuron (LMN) weakness (see table):

UMN (cortex, corticospinal tracts to spinal cord): Often affects UE extensors/LE flexors → posture of UE flexion/LE extension LMN (anterior horn cells, nerve roots, peripheral nerves, NMJ, muscle): Distribution varies based on lesion; segmental (anterior horn cell, nerve root), focal (mononeuropathy), diffuse (peripheral nerve, NMJ, myopathy); to determine nerve root vs. peripheral nerve (see “Peripheral Neuropathy”) Sensory sx can be present or absent in either LMN or UMN (nonspecific)

If strength impaired, localize the lesion:

 

Upper Motor Neuron versus Lower Motor Neuron Signs on Exam
	UMN	LMN
Strength	↓	↓
Tone	↑	↓ or Normal
Muscle Bulk	Normal	↓
Fasciculations	No	Yes
Reflexes	↑	↓
Plantar response (Babinski sign)	↑	↓

Labs: Consider Na, K, Phos, Mg, Ca, CK, TSH, B1₂, LDH, LFTs, acetylcholine receptor antibodies, neuropathy w/u (see “Peripheral Neuropathy”)

Imaging:

Head CT: If concern for acute intracranial process w/ UMN weakness (stroke/ICH) Spinal MRI: Appropriate with subacute to chronic UMN pattern weakness; consider appropriate spine imaging if UMN or LMN weakness & associated symptoms of trauma (complete spine), neck pain (cervical spine), low back pain (lumbar spine)

Other:

EMG/NCS: An extension of the neuromuscular exam; helpful to localize and characterize severity & temporal stage of nerve root, peripheral nerve, NMJ, or muscle disease Muscle bx: Helpful in assessing etiology of myopathy/myositis

Differential Diagnosis (Semin Neurol 2011;31:115)

 

Selected Differential Diagnosis of Muscle Weakness
Diagnosis	Clinical Features
Stroke, ICH	Acute onset UMN pattern weakness

 

Spinal cord lesion	Sensory level, crossed sensory sx (e.g., absent ipsilateral light touch, absent pain & temp contralateral), bowel or bladder dysfunction
Motor neuron disease (ALS)	Distal segmental painless weakness & atrophy; UMN + LMN signs (may be later in clinical course)
Myasthenia gravis	Fatigable weakness, often w/ ptosis, diplopia, dyspnea, or generalized weakness
Myositis (PMR, DM)	Proximal symmetric weakness, ± muscle pain, can be assoc w/ heliotropic rash in DM, often ↑CK
Mononeuropathy (see “Peripheral Neuropathy”)	Focal weakness (e.g., foot drop) w/ sensory loss

Treatment

As per underlying disorder; if true weakness present & dx unclear or neuro cause established → Neurology referral

If red flags present (above) or other concern for acute intracranial process → ED

 

Background (Continuum 2012;18:13; Neurology 1993;43:817)

Definition: Peripheral nervous system: nervous system outside of CNS (brain & spinal cord); consists of somatic (sensory & motor) & autonomic nerves

Peripheral neuropathy: Diseases affecting cell body or processes of the lower motor neuron (motor) or dorsal root ganglia (sensory) or paraverterbral/preverterbral ganglia (autonomic)

Pathophysiology: Pattern of nerve injury varies with mechanism; peripheral neuropathy may affect single or multiple types of nerve Epidemiology: Peripheral neuropathy affects ~2–8% of US adults & 21% of DM pts presenting to PCP office

Etiology: Damage to nerves may be inflammatory, vasculitic, traumatic, toxic, metabolic, or infectious—careful hx & exam determining pattern of lesions can help w/Ddx

 

Class	Site of Damage	Example (w/ example etiology)
Radiculopathy	Nerve root (e.g., C7)	C7 radiculopathy (Spinal DJD)
Mononeuropathy	Individual nerve (e.g., median nerve)	Carpal tunnel syndrome (Trauma/pressure)
Mononeuropathy multiplex	Multiple individual nerves	Foot drop & wrist drop (Vasculitis)
Polyneuropathy	Diffuse, typically symmetric, often length-dependent	Burning/dysesthesia in feet (EtOH)

Evaluation (Continuum 2012;18:139)

General approach: First, characterize pattern of neuropathy (sx, onset, distribution); second, look for etiologic clues (PMHx, soc hx, meds, diet, occ hx)

Characterize neuropathic pattern:

Sensory sx: Paresthesias, allodynia (typically nonpainful stimuli → painful), hyperalgesia (↑ sensitivity to painful stimuli), difficulty distinguishing hot vs. cold, ↓ proprioception (often more noticeable when no/low ambient light or when no visual clues) Predominantly sensory etiologies: DM, B₁₂ deficiency, HIV, amyloid, leprosy,

Sjögren’s, sarcoid, uremia, paraneoplastic Motor sx: Weakness (see “Weakness”), fasciculations, weakness, atrophy.

Predominantly motor etiologies: GBS, CIDP, porphyria, lead, botulism Autonomic sx: Orthostasis, gastroparesis, constipation, bladder or ED, hypoglycemic unawareness in DM

Onset: Acute (GBS, vasculitis, infection) or subacute, chronic (toxin, vitamin deficiency, neoplastic, metabolic, CIDP) Distribution: Peripheral or proximal? Symmetric or asymmetric?

Etiologic clues:

Assoc sx: Fever, constitutional sx, thyroid sx, rash, HA, N/V, dry eyes/mouth, recent illness PMHx: DM, HIV, amyloid, CKD/ESRD, cancer, sarcoid, autoimmune disease, malabsorption syndrome (celiac, IBD, gastric bypass), HCV (seen in cryoglobulinemia), thyroid disease, amyloid; consider leprosy, Chagas in appropriate populations (Continuum 2012;18:126) Social hx: EtOH use (known toxic if >7 drinks/d, diet (vegan [B₁₂ def]), carnivorous fish (ciguatera

 

toxin), solvent use/abuse (“huffing”) Meds/toxins: Generally cumulative; a dose-and/or time-dependent process (see below) Other: Occupational hx (lead, solvent, grout exposure), FHx

 

Medications/Toxins/Vitamins Associated with Neuropathy (Continuum 2012;18:139)
Anti-infective	INH, MNZ, nitrofurantoin, chloroquine, FQs, ethambutol
Immunosuppressants	Etanercept, infliximab, leflunomide, tacrolimus
Other	Colchicine, disulfiram, thalidomide, dapsone, phenytoin
Toxins	Arsenic, gold, lead
HAART	Didanosine, stavudine, zalcitabine
Cardiovascular	Amiodarone, hydralazine, ?statins
Oncologic	Cisplatin, docetaxel, paclitaxel, suramin, vincristine (vinblastine)
Vitamins	Vit B1 deficiency, vit B6 (deficiency or excess), vit B12 deficiency, vit E deficiency (malabsorption syndromes), Copper deficiency, Zinc excess

Exam: VS (orthostatics), e/o systemic disease (cachexia, atrophy, orthostatics, hyperpigmentation, skin/nail/hair changes, organomegaly, ulcers, nerve hypertrophy)

Full neuro exam, looking for e/o central process (CN involvement, ataxia, hyperreflexia); motor exam (see “Weakness”) & sensory exam: Pinprick, proprioception (large fiber sensory involvement); gait for foot drop

Provocative tests: Test which provokes or exacerbates pt symptoms; suggestive of nerve entrapment or compression

Tinel: For mononeuropathy; lightly percuss over the nerve

Phalen’s: For median neuropathy (CTS); pt holds dorsum of hands pressed together w/wrist flexion Spurling: For cervical radiculopathy: have pt extend neck and tilt toward affected side, then provide axial pressure → worsening symptoms (Clin Orthop Relat Res 2012;470:2566) Straight leg raise: For lumbosacral radiculopathy: pt supine, knee extended, and provider passively lifts straight leg raise (hip flexion) → radicular pain (not hamstring discomfort) in ipsilateral or contralateral leg

 

Site of Injury & Distinguishing Features	Sensory Distribution
Median Nerve (Carpal Tunnel Syndrome) Hx: Occupational wrist overuse Motor: Thenar eminence wasting Tests: Tinel’s over volar wrist, Phalen’s CTS may spare palm (palmar branch does not go in carpal tunnel)
C6 Root Motor: Primary nerve root for supination (biceps, brachioradialis) Tests: ⊕ Spurling’s DTR: Biceps, brachioradialis C6 dermatome includes radial aspect of forearm
Radial Nerve Hx: “Saturday night palsy”; compression in spiral groove of humerus due to sleeping position (arm over chair or pt/companion’s weight on arm), often assoc w/ deep sleep of intoxication Motor: Wrist/finger extension
C7 Root Motor: Primary nerve root for elbow extension, also pronation, wrist/finger flexion Tests: ⊕ Spurling’s DTR: Triceps C7 dermatome includes posterior arm, forearm
Ulnar Nerve (elbow > wrist) Hx: Elbow pain, elbows resting on hard surface (WC, desk); handlebars (wrist) Motor: Usually mild hand weakness; → “claw hand” Tests: For elbow compression (most common),

 

⊕ Tinel’s over medial cubital tunnel (btw olecranon & medial epicondyle)
Common Lower Extremity Neuropathies
Lateral Femoral Cutaneous Nerve Neuropathy (Meralgia Paresthetica) Hx:Tight pants/belts, pregnancy, obesity (compression as exits pelvis to lateral thigh) Sensory only; can be anterior thigh as well
L5 Root Motor: Hip abduct, ankle dorsiflex, 1st toe ext, foot inversion + eversion Gait: Trendelenburg gait (2/2 weak hip abductors), foot “slap” (2/2 poor dorsiflexion) DTR: ± Achilles Tests: ⊕ Straight leg raise Sensory: First dorsal webspace and lateral calf most consistent
Site of Injury & Distinguishing Features	Sensory Distribution
S1 Root Motor: Ankle plantarflex, knee flex Gait: heel slap gait (2/2 weak plantarflexion) DTR: Achilles Tests: ⊕ Straight leg raise

 

Sensory: Lateral heel, posterolateral calf most consistent
Peroneal/fibular Nerve (proximal fibular head > foot) Hx: Crossing legs at knee, injury at ankle/tight shoes (for deep branch) Motor: Foot drop (impaired ankle eversion/dorsiflexion) Sensory: dorsum of foot/lateral ankle; if distal injury, only dorsal webspace between 1st- 2nd digits

Labs: For polyneuropathy or idiopathic mononeuropathy: CBC, Cr, HbA1c/fasting glucose, B₁₂ (see “Folate and Vitamin B₁₂ Deficiency”), TSH, SPEP + immunofixation; consider HIV, RPR, ANA, ESR, HBV, HCV, anti-TTG/gliadin, heavy metal screen, Lyme, rheumatologic tests

depending on clinical picture

EMG/NCS: Usually w/ neurology guidance, not needed for all pts; used to assess disease severity, assist in localization, or further characterize type of neuropathy (demyelinating vs. axonal neuropathy)

Imaging: MRI if concern for radiculopathy or plexopathy

Red flags: Rapidly progressive, ascending, areflexia, following flu- like/diarrheal illness or immunization (GBS), back pain, progressive, bowel/bladder Δs, saddle anesthesia, ↓ rectal tone (cord compression), painful, multiple noncontiguous nerve involvement (vasculitis)

Differential Diagnosis

Distal symmetric polyneuropathy: Most common type of peripheral neuropathy; due to axonal damage; Etiologies: DM, HIV, EtOH,

 

medication-induced, idiopathic, ESRD; Features: “Stocking-glove distribution” due to axonal length-dependent; hand sx begin once leg sx have “reached” knees; slowly progressive, painless or painful; Eval: Labs as above, consider NCS

Length-independent polyneuropathy: Suggests demyelinating disease; Features: Early proximal sx or ↓ reflexes; multiple nerves affected, can be symmetric or asymmetric; Etiologies: GBS, CIDP, Lyme, HIV, sarcoid, amyloid, paraneoplastic, genetic d/o

Autonomic neuropathy: DM, amyloid, GBS, Sjögren, Fabry disease; Eval: Consider autonomic function testing, gastric emptying study Small fiber sensory neuropathy: Length-dependent distribution of neuropathic pain despite otherwise normal neuro exam & nerve conduction studies; due to DM, autoimmune, paraneoplastic, Celiac disease; may be confirmed w/skin biopsy

Mononeuritis multiplex: Multiple nerves affected, often in stepwise, asymmetric fashion; Etiology: Vasculitis, Sjögren’s, sarcoid, DM, Lyme Mononeuropathy: Focal lesion of a single nerve; compression/entrapment most common; can also be due to trauma, Lyme, or DM; presents w/ numbness & paresthesias; consider radiculopathy as well (see table below); Eval: EMG/NCS to localize/quantify injury in severe/refractory/idiopathic cases; consider w/u for DM, thyroid, arthropathies; Tx: Reduce external compression as able (ergonomics/behavioral changes, wrist splints at night for CTS); if severe, refractory, involves motor function, consider surgical referral Radiculopathy: Majority 2/2 nerve root compression due to DJD spine, also DM, Lyme, zoster, sarcoid, tumor infiltration; sx often assoc w/ or preceded by neck (cervical) or low back (lumbar) pain which may then radiate into limb, numbness in dermatome(s) and weakness in myotome(s); see table for most common; Eval: EMG/NCS to localize/characterize injury; MRI of appropriate spine region; consider w/u for nondegnerative cause if hx suggests; Tx: Neuropathic pain Rx, rest, & exercise therapy; limited data for epidural steroid injections; surgical referral for refractory pain & weakness w/ evidence of structural cause on MRI

Diabetic neuropathy (NEJM 2005;353:392; AFP 2008;78:835; Med Clin N Am

2009;93:285)

Half of pts w/ DM will develop neuropathic complications; distal

 

symmetric polyneuropathy most common; counsel pts re: ulcer avoidance (7× ↑ risk if neuropathy); see “Diabetes”

Autonomic neuropathy: ↑ Risk hypoglycemic unawareness & cardiac arrhythmia

Treatment-related neuropathy (“insulin neuritis”): Acute, painful/sensory, occurs when poorly controlled → tight control, typically in DM1; assoc w/ autonomic sx or severe wt loss; resolves over several mo; can recur

Lumbosacral radiculoplexus neuropathy (“diabetic amyotrophy”): Abrupt onset of severe unilateral thigh pain followed by atrophy & weakness; usually distal > proximal; assoc w/ wt loss; improves over mos, may have significant residual deficit; DM2 > DM1; consider EMG/NCS, which show radiculopathy/plexopathy

Focal neuropathies: Assoc w/ CN palsies (see “Diplopia”), thoracic radiculopathies

Treatment (Continuum 2012;18:161)

General approach: Avoid neurotoxic agents; treat underlying cause as possible

Pain: Multiple agents available (below); opioids: Limited role (see “Chronic Pain”)

 

Neuropathic Pain Treatment
Medication Class	Example Rx	Notes
TCAs	Amitriptyline 10–25 mg QHS (max 150 mg QD) Nortriptyline 10–25 mg QHS (max 100 mg QD)	Evidence: Level A for DM, postherpetic neuralgias S/e: Dry mouth, constipation, orthostasis, urinary retention; caution if CAD, glaucoma, sz, LUTS
SNRI	Duloxetine 30 mg QD (max 60 mg BID)	Evidence: Level A for DM S/e: Nausea, ↑ BP; caution if liver dz, HTN
Ca channel ɑ-2- δ ligands	Gabapentin 300 mg QD; max 1200 mg TID Pregabalin 25–75 mg QD; max 300 mg BID	Evidence: Level A for DM, postherpetic neuralgia, cancer pain (gabapentin) S/e: Sedation, dizziness, edema, wt gain Renally cleared, caution if ↓ GFR
Lidocaine patch	1–3 patches; Apply 12 h on, 12 h off	Evidence: Level A for postherpetic

 

		neuralgia S/e: Local itch, rash; systemic abs possible (do not apply heating pad over patch)
Capsaicin patch/crm	Crm TID–QID to affected area (results after 2 wk) Alt: Topical anesthetic, then 1–4 patches × 60 min q3mo	Evidence: Level A for HIV, postherpetic neuralgia S/e: Pain, erythema (↓ w/ ongoing use)
Tramadol	50 mg QD; max 400 mg QD (ER)	Evidence: Level A: DM, phantom pain S/e: N/V, constipation, dizziness, sedation; avoid if substance use d/o, suicide risk

When to refer: Neurology referral for any mod–severe disease unless typical slow distal symmetric polyneuropathy; if red flags present (above) pts should be referred to ED

 

Background (AASM ICSD-2 2005; Neurol Clin 2012;30:1137)

Definition: Disorder characterized by (1) Urge to move limbs assoc w/ paresthesias, (2) Sx worse at rest, (3) Sx worse at night, (4) Physical activity provides partial relief (Sleep Med 2003;4:10):

Etiology: Often idiopathic but can be assoc w/ systemic disease, pathophysiology thought to be DA-related, possibly due to ↑ of dopaminergic transmission → postsynaptic desensitization (BMJ 2012;344:e3056); genetic predisposition has also been implicated (⊕ FHx in 15–58% of pts)

Epidemiology: Some degree of RLS affects 5–15% of adults, ~2% of adults affected enough to require tx; prevalence ↑ w/ age (up to 20% in pts >80 y); more common in Caucasian ethnicity, ♀ > ♂ (2:1) (Arch Intern Med 2005;165:1286)

Risk factors: Has been assoc w/ Fe deficiency, ESRD/uremia, DM, MS, PD, autoimmune disease, OSA, venous insufficiency, & pregnancy

Evaluation

History: Pt typically presents complaining of features above; can also

 

c/o insomnia, bedmate may endorse periodic limb movements of sleep (occurs in 80–90% of pts w/RLS); ⊕ FHx

Single question w/ Se/Sp 100/96% for dx of RLS: (Eur J Neurol 2007;14:1016) “When you try to relax in the evening or sleep at night, do you

ever have unpleasant, restless feelings in your legs that can

be relieved by walking or movement?” Medications/Toxins: Agents can induce/worsen RLS: Antidopaminergic (antipsychotics), diphenhydramine, TCAs, SSRIs,

mirtazapine, EtOH, caffeine, lithium, βBs

Exam: In isolated RLS, should be normal

Diagnostics: ✓ Iron studies (incl ferritin) & CBC; w/u for 2° causes as indicated; may consider polysomnography if dx unclear

Treatment (Sleep 2012;35:1039; JAMA Intern Med 2013;173:496; Mayo Clin Proceed

2004;79:916)

General approach: Treat 2° causes when possible (OSA, Fe deficiency); offer nonpharmacologic tx to all pts; further tx indicated for pts w/ frequent or >mod discomfort

Iron supplements: Oral supplements may ↓ sx in pts w/ Fe deficiency (ferritin <75 ng/mL), ✓ ferritin after 3 mo, can then follow every 3–6 mo Nonpharmacologic treatment; cognitive/behavioral tx & exercise may

↓ RLS sx; avoid aggravating factors/exacerbating meds/toxins as able; trial of brief walking, hot baths, or leg massage before bedtime (BMJ 2012;344:e3056); counsel pts on sleep hygiene; no strong evidence for efficacy of LE compression devices

Dopamine agonists: Pramipexole, ropinirole are 1st-line, effective, well-tolerated (lower risk of complications than Levodopa)

S/e: Nausea, dizziness, somnolence, nasopharyngitis; ↓ impulse control, vivid dreams Dosing: Either agent should be taken ~2 h prior to sx onset, renal dosing adjustments Example Rx: Ropinirole

0.25 mg QHS; may ↑ by 0.25 q2–3d as needed (max 4 mg) or Pramipexole 0.125 mg QHS; may ↑ by 0.125 q2–3d until relief obtained (max 2 mg)

Gabapentin/Pregabalin: Less evidence for efficacy, but consider if coexisting neuropathic pain or in pts w/ mild sx; s/e include somnolence; adjust dose in CKD

Other treatments: Typically initiated by neurologist for refractory

 

cases; levodopa effective but risk of augmentation (earlier/quicker/more severe sx, ↓ duration of med effect) → used in pts w/ intermittent sx; clonidine, BZD, & opiates rarely used

When to refer: Refractory disease or dx unclear → neurology Patient information: ninds.nih.gov/disorders/restless_legs/detail_restless_legs.htm

 

Background (JAMA 2003;289:347; Continuum 2016;22:1143)

Definition: Rhythmic, oscillatory, involuntary movement with a constant frequency; usually classified into resting vs. action tremor (below) Resting tremor: Evident when affected body part not voluntarily activated & remains supported against gravity (e.g., hand on lap; most commonly seen in parkinsonism)

Action tremors:

Postural: Occurs when head/limbs are held in a fixed posture against gravity Kinetic: ↑ By voluntary movement; intention tremors ↑ during goal-directed movement

History: Should include age of onset, evolution of sx over time, body regions involved, maneuvers that elicit or suppress tremor, review of tremor-exacerbating substances (caffeine, tobacco, EtOH w/d), hyperthyroid sx, medication list (bronchodilators, SSRI, SNRI, antipsychotics, stimulants, lithium, VPA, prednisone), ⊕ FHx

Exam: Postural: Assess w/ sustained arm extension

Kinetic: Assess with finger-nose-finger, asking pt to draw spirals or write their name, drink from a cup; ⊕ intentional component if tremor worsens as approaches target (e.g., as finger approaches nose in finger-nose-finger) Resting tremor: Evaluate while pt seated & standing; look for tremor of head, jaw, tongue, and voice (sustained phonation) Psychogenic: Look for distractability (finger tapping w/ opposite hand), entrainment (tremor → line with specific rhythm), suggestibility

Common Tremor Syndromes

 

Tremor Characteristics
Type	Rest	Postural	Kinetic
Physiologic		++	+
Essential tremor	±	++	++
Parkinsonian	++	+	±
Dystonic	±	++	++
Neuropathic		++	+
Cerebellar		±	++
Psychogenic	+	+	+

±, Occasionally present; +, may be present; ++, typical (Adapted from Postgrad Med J

2011;87:623)

Enhanced physiologic tremor (AFP 2003;68:1545): All persons have some degree of postural tremor; enhancement of this is most common cause of action tremors

S/sx: Low amplitude, high frequency (~10–12 Hz); best visualized by holding arms outstretched w/ fingers spread apart Etiologies: ↑ Sympathetic activity (anxiety, fear), endocrinopathy (hyperthyroidism, hypoglycemia, hypercortisolism, pheo), drugs (caffeine, lithium, TCAs, SSRIs, corticosteroids, valproate, theophylline, amphetamines), withdrawal (EtOH, BZD) Tx: Underlying condition; also responds to propranolol (can be used in stressful social situations & for performance anxiety)

Essential tremor: Very common (up to 5% prevalence), progresses w/ age & can → substantial disability (Postgrad Med J 2011;87:623)

S/sx: Usually bilateral (but may be slightly asymmetric), 4–8 Hz postural action tremor; 50% are intentional; most frequently starts in hands/arms (95% of pts), usually progressive; can also affect head (“yes-yes” or “no-no” sign= “titubation”), jaw, voice, rarely legs (Neurology 2005;64:2008); can improve after EtOH consumption Etiology: Genetic component, FHx in ~50% cases (autosomal dominant pattern) Tx: 1st-line agents are propranolol & primidone

→ avg tremor ↓ by 50%

Propranolol: Dose range 60–320 mg/d (avg ~185 mg/d); s/e: Lightheadedness, fatigue, impotence, bradycardia (Neurology 2005;64:2008) Primidone: Dose range 50–1000 mg/d (avg ~480

 

mg/d); s/e: Sedation, nausea, dizziness/unsteadiness, confusion Other tx: BZD, gabapentin, or topiramate are 2nd line, refractory & severe cases may benefit from neurosurgical intervention (DBS or ablation)

Cerebellar tremor: Intention tremor, large amplitude, ↑ as limb moves closer to a target (e.g., finger-to-nose, heel-to-shin); assess for other cerebellar signs (dizziness, nystagmus, dysmetria, ataxia) → imaging (urgently if new finding)

Other:

Parkinson disease: Asymmetric resting tremor affecting UE, LE, or both (if both, typically on same side); wrist pronation–supination common; can affect jaw (closed/resting > open/talking); can also have emergent postural/kinetic tremor, if present, generally ↑ amplitude than essential tremor; see “Parkinson Disease”

Dystonic tremor: Assoc w/ dystonia (sustained abnormal posture), can improve by touching affected region Orthostatic tremor: Rare; limited to legs & trunk, occurs exclusively while standing (e.g., legs giving out while waiting in line) Psychogenic tremor: Contains rest, postural, & action components; inconsistent features, may have variable frequency or change direction; may be paradoxically worse with “loading” (pressing down on affected extremity); see “Somatoform Disorders”

Drug-induced: Can be resting (antipsychotics) or action tremor (bronchodilators, stimulants); trial off offending agent as able to confirm etiology; may consider propranolol for action tremor or DA for resting tremor if very bothersome but cannot d/c med; (Continuum 2016;22:1143) continue neurology c/s prior to tx

 

Background

Definition: Movement disorder syndrome characterized by “TRAP”: Tremor, Rigidity, Akinesia/bradykinesia, & Postural instability Pathophysiology: Progressive neurodegenerative d/o; idiopathic, thought 2/2 ↓ DA in substantia nigra (Lancet 2009;373:2055)

 

Epidemiology: 2nd most common neurodegenerative disease, affects

~1% of US adults >60 y (Neurology 1995;45:2143); incidence ↑ w/ age; affects ♂ > ♀ (NEJM 2005;353:1021); significant cause of morbidity & disability in the elderly

Natural history: Average pt → disability (not independent w/ ADLs) ~7 y after dx, but variable; often heralded by increasingly severe gait disability (Mov Disord 2008;23:790); presence of hallucinations strong predictor of SNF placement (J Am Geriatr Soc 2000;48:938); Poor prognosis: Rigidity/hypokinesia (rather than tremor) as presenting sx predict more rapid disease progression (Mov Disord 1996;11:236)

Other parkinsonian syndromes (Neurol Clin 2001;19:607): Less responsive to dopaminergic therapy and more rapid progression; syndromes include:

Progressive supranuclear palsy (early falls, axial rigidity, vertical gaze palsies); Multiple system atrophy (prominent autonomic sx & cerebellar signs), dementia with Lewy bodies (visual hallucinations), corticobasal degeneration

Secondary causes of parkinsonism (Lancet 2009;373:2055)

Medications: Metoclopramide, compazine, antipsychotics, CCBs, possibly SSRIs Toxins: CO, cyanide, manganese, MPTP (street opioid contaminant)

Vascular: small vessel strokes

Other: Infection (encephalitis, HIV), metabolic (Wilson, hypoparathyroid), head trauma

Evaluation (JAMA 2003;289:347; NEJM 2005;353:1021)

Diagnosis: Clinical diagnosis: eval w/ careful hx & neuro exam (including gait assessment)

History: Determine onset and progression of sx; PMHx; HIV, stroke risk factors (vascular parkinsonism); medication list (drug-induced parkinsonism)

 

Typical Presentation of Parkinson’s Disease
Tremor	Initial presentation in ~70% of pts; typically occurs at rest; asymmetric, slow (4–6/s), “pill-rolling” of 1 hand
Rigidity	↑ tone, cogwheeling, worse when pt performing repetitive movements w/ contralateral limb

 

Bradykinesia, akinesia	Initial c/o can be “weak” or “clumsy” limb; major cause of disability in PD: Observe during interview & assess w/ toe or finger tapping (pt will have ↓ amplitude & irregular cadence)
Postural instability or gait disorder	Pt can c/o impaired balance, ↑ falls; ↓ arm swing on exam; shuffling gait, stooped posture at later stages
Other sx	Depression, sleep disturbances (daytime hypersomnolence, restless leg syndrome), hypophonia, micrographia, muscle aches, orthostasis, dysphagia, cognitive changes (↓ executive function), ↓ olfaction

Diagnostics: Not routinely required, can consider MRI if atypical presentation

Levodopa challenge: Improvement w/ carbidopa/levodopa → 70.9% Se, 81.4% Sp for predicting eventual dx of PD (Mov Disord 2002;17:795) Features which suggest an alternative diagnosis at onset: ↑ falls and ↓ tremor, symmetric onset, rapid progression, poor response to dopaminergic therapy

Treatment (Neurology 2006;66:983)

Referrals: All pts w/ suspected parkinsonism should be referred to neurology or a movement d/o specialist; PT, OT & home safety assessment usually indicated

Pharmacologic Rx: No current tx options to slow progression; Rx below intended to ↓ sx & to ↑ function; all typically prescribed by neurologist/specialist

Dopaminergic agents: Dopamine (levodopa/carbidopa) or dopamine agonists (ropinirole, pramipexole) typically 1st-line; tolerance & disease progression → ↑ doses over time S/e: GI sx (N/V, abdominal pain), dizziness, orthostatic HoTN, hallucinations, impulsive behavior (e.g., pathologic gambling), vivid dreams, insomnia, dystonia, dyskinesias Other agents: Catechol-O– methyltransferase inhibitors (entacapone), MAOI (selegiline, rasagiline), anticholinergics (frequent s/e), amantadine

On–off phenomenon: (motor fluctuations) “On” effect immediately after taking med → excessive movements, dyskinesias; “Off” effect ~4 h later, as dopaminergic effect wears off → freezing, prominent rigidity; often managed w/ adjunctive tx (rasagiline, entacapone, pramipexole, & ropinirole all shown to ↓ “off” time, at expense of ↑ “on” sx)

Deep brain stimulation: Implantation of electrodes in subthalamic

 

nucleus or globus pallidus; Indications: Pts w/ intractable motor fluctuations who are levodopa responsive & neuropsychiatrically intact w/o dementia; can → ↓↓ motor sx

MANAGEMENT OF COMORBIDITIES

 

(Mov Disord 2005;20:958; Biol Psych 2002;17:1031)

Assessment of home safety & safety w/ activities (driving, ambulating) crucial as functional status ↓: involve PT/OT, low threshold for SLP swallowing eval/ speech therapy, consider aspiration precautions

Counseling and support: Given disease course, recommend for spouse as well; review advance directives (see “Advance Care Planning”)

Depression: 40–50% of PD pts; consider TCAs, paroxetine, venlafaxine; SSRI contraindicated if using MAOI (Cochrane Database Syst Rev 2003;3:CD003465)

Sleep disturbance: Many manifestations, including insomnia, daytime hypersomnolence w/ sleep attacks, restless legs syndrome (see “Restless Legs Syndrome”), excessive limb movements during sleep, REM sleep d/o; provide counseling about sleep hygiene to pt and spouse, identify causes of poor nocturnal sleep (see “Insomnia”), can consider modafinil for daytime hypersomnolence (limited evidence) Psychotic sx: Can be 2/2 PD or dopaminergic tx; paranoia & hallucinations in ~40% of PD pts, frequently 2/2 PD meds or underlying dementia, consider antipsychotics only after r/o toxic/metabolic cause &

? trial of ↓ dopaminergic med dose; avoid typical antipsychotics (DA antagonists worsen motor sx); quetiapine or clozapine preferred, should be comanaged w/ neurologist; see “Dementia”

Dementia: Consider anticholinesterases (rivastigmine, donepezil) (NEJM

2004;351:259)

Falls: ↑ Risk if BZD use, prior falls, advanced disease, ⊕ Romberg (J Neurol 2001;248:950) → early home safety eval (see “Falls”)

GI tract dysmotility: ↑ Risk constipation & aspiration 2/2 brainstem + enteric nerve dysfunction; consider stool softeners

Sialorrhea: ↑ drooling 2/2 dysautonomia & ↓ motor control, chewing

 

gum use might help in mild cases, for severe sx consider anticholinergic Rx or referral for Botulinum injections

Orthostasis: Common in late stage PD, can be worsened w/ levodopa; 1st remove other offenders (βBs), encourage fluid/salt intake, try compression stockings; may consider fludrocortisone ± midodrine Patient information: parkinsons.org.uk/?page=10495w

 

Background (Neurology 2011;77:1005; Epilepsia 1975;16:1)

Definitions: Seizure: Symptomatic episode of abnormal electrical activity in brain; can be generalized (onset in both hemispheres) or focal (part of 1 hemisphere); focal seizures may or may not → impairment of consciousness/awareness; Epilepsy: Seizure disorder;

≥2 unprovoked seizures; Status epilepticus: Seizure lasting >5 min or multiple seizures over >5 min period w/o interval return to baseline Epidemiology: 6% of population will experience a seizure in their lifetime; epilepsy affects 2 million in US

Risk factors: ⊕ FHx, perinatal injury, childhood febrile seizures, head trauma, CNS infection, stroke, brain tumor, ICH

Provoked seizure: Due to discrete, temporary trigger rather than underlying seizure d/o

Etiologies: Idiopathic/unknown, structural, metabolic, genetic, perinatal, infection (encephalitis, meningitis, cysticercosis), neoplasm, stroke, ICH, trauma, EtOH or BZD withdrawal

Differential dx: Syncope (up to 90% pts w/ syncope have myoclonic jerks during event), physiologic sleep myoclonus (“jerk” when asleep/falling asleep), sleep d/o, complex migraines, movement d/o, limb shaking TIA, transient global amnesia, & nonepileptic seizures (aka pseudoseizures; frequently coexist w/ epilepsy, in up to 10–30%)

Evaluation (AFP 2007;75:1342; Postgrad Med J 2009;85:667; BMJ 2012;345:e4576)

General approach: For 1st-time seizure, determine (1) was it a true seizure and if so (2) was it provoked; for recurrent/worsening epilepsy, attempt to determine cause of worsening

History: Was it a seizure?: From pt/witness: preceding aura (epigastric

 

sensation, bad smell), focal vs. generalized onset, duration, tonic and/or clonic movements

Features suggesting seizure: Tongue biting, head turning, cyanosis, postictal confusion, incontinence, eyes open during event w/ forced gaze deviation

History: Was it provoked? Why now?

PMHx: Seizure RF: TBI, febrile seizures, metabolic d/o (hyponatremia, hypoglycemia/DM on hypoglycemic agents), SLE, developmental delay Meds: Can ↓ seizure threshold; Anti- infectives: FQs, high-dose β-lactams, INH, MNZ, chloroquine, mefloquine; Analgesics: Tramadol, opiates, meperidine; Psych: Bupropion, clozapine Associated symptoms/processes: Current illness, liver or renal dysfunction, UTI; ↓ sleep Features suggesting provoked seizure: EtOH or BZD w/d, cocaine/methamphetamine use, head injury, CNS infection, stroke, eclampsia; n.b. seizure after sleep deprivation considered unprovoked

Exam: Full neuro exam (frequently nl); tongue & extremities for ictal injuries; skin exam for e/o neurocutaneous d/o (tuberous sclerosis, neurofibromatosis, Sturge–Weber)

Studies: CBC, lytes, glucose, tox, pregnancy test; (note that GTCs may transiently ↑ lactate, CK, & WBC); ✓ ECG to exclude arrhythmia EEG: All pts w/ new seizure; predicts sz recurrence, characterizes epilepsy syndrome; Se ~50%, ↑ if w/in 24 h Imaging: All pts w/ new seizure; MRI w/ contrast preferred, seizure protocol

Pt w/ known epilepsy: Ask about typical seizure presentation, frequency of seizures, current AED/prior AED regimens, triggers for prior seizures (e.g., ↓ sleep)

Pt w/ epilepsy reporting ↓ control of disease from baseline (recurrent seizure/↑ seizure frequency): Are episodes(s) similar to prior seizures? Adherence to AED regimen? New meds started or current toxic/metabolic process? ✓ AED levels if applicable; unless new seizure type, new neuro sx, or known brain mass/infectious etiology (e.g., neurocysticercosis), no imaging required

Management (Continuum 2010;16(3):105)

 

If provoked single seizure → treat underlying cause

All pts: Avoid meds/processes that ↓ seizure threshold (above)

Antiepileptic drugs: Initiated & managed by neurology

Indications: For all pts w/ >1 seizure or structural abnormalities, abnl EEG or neuro exam Relative indication: Pts w/ 1 seizure and no structural/neuro abnormalities, but ↑ risk of sz complication or per pt preference; starting AEDs after 1st seizure → ↓ sx recurrence over next 2 y, but no effect on long-term recurrence/remission rate Regimen/agent: Monotherapy is goal; AED chosen based on sz type, age, comorbidities, med interactions (review prior to PCP initiation of new meds, esp if pt on carbamazepine, phenytoin, valproic acid) & s/e profile S/e: Sedation common; all AEDs may ↑ suicidal thoughts → monitor pts for SI

Counseling (Postgrad Med J 2009;85:667)

Driving: Laws vary by state, most require sz-free period × 3–18 mo; some states require providers to report directly to DMV (CA, DE, NV, NJ, OR, & PA), list at: http://www.epilepsy.com/driving-laws

Safety: Counsel not to swim alone, avoid bathtubs; caution near fire, working at heights, operating dangerous machinery, extreme sports Triggers: Importance of minimizing EtOH/drugs, sleep deprivation, med nonadherence, including missed doses

Antiepileptic Medications (Continuum 2010;16(3):121)

 

Medication	Monitoring	Side Effects
Carbamazepine	✓ CBC, LFT, lytes; CYP450 inducer (↓ concentration of other Rx such as warfarin, OCPs); avoid w/ MAOI, ↑ SJS incidence in pts of Asian descent	↓ Na, ataxia, cytopenias, aplastic anemia, agranulocytosis, rash, SJS
Phenytoin	CYP450 inducer (as above); ✓yearly DEXAs; avoid in pts w/ bradycardia/heart block	Ataxia, nystagmus, hirsutism, gingival hyperplasia, ↑ LFTs, ↓ BMD, blood dyscrasias, SJS
Valproate	✓ CBC, LFT, lipase; good for pts w/ migraine, bipolar, depression; avoid in hepatic dx, young women	Teratogen; tremor, ↓ hair, ↑ wt, N/V, ↓ PLT, ↑ LFTs, ↑ NH3, ↓ BMD, pancreatitis, blood dyscrasias
Oxcarbazepine	✓ Na; CYP450 interact (↓ OCPs); contraind in generalized sz	↓ Na, apathy, confusion, acne
Lamotrigine	Slow titration required → d/c at 1st	Rash, SJS, diplopia, ataxia, blood

 

	sign of rash; good for pts w/ bipolar, chronic pain, elderly	dyscrasias
Levetiracetam	Caution w/ depression, bipolar; dose adjust w/ CKD	Irritability, aggression, emotional lability, anxiety, depression, SI
Topiramate	Avoid in pts w/ kidney stones; CYP450 interact (↓ OCPs); good for pts w/ migraine, obesity	Cognitive dysfunction, fatigue, ↓ wt, tingling, kidney stones
Zonisamide	Avoid in pts w/ kidney stones	Cognitive dysfunction, kidney stones, ↓ wt, ataxia, blood dyscrasias, SJS
Lacosamide	Contraindicated in pts w/ AV block	↑ PR interval; AF

When to Refer

Neurology: New unprovoked sz, pts on >1 AED, or no response to meds; pts w/ diagnosis of epilepsy should be established with neurologist; if not → refer

Emergency department: If suspicion of CNS infection, fever or immunocompromised → ED for LP; if new neuro deficits or not back to baseline (? of status epilepticus) → ED for urgent imaging (r/o ICH, stroke, tumor)

 

Background (Circulation 2012;125:e2; MMWR Weekly 2012;61:379; Circulation

2016;133:e388)

Definitions: Stroke: Loss of brain function 2/2 disruption of cerebral blood supply; can be ischemic (occluded blood vessel; 87% of all strokes), or hemorrhagic (disrupted/ruptured blood vessel; 13% of strokes)

Transient Ischemic Attack (TIA): Transient (<24 h) episode of neurologic dysfunction 2/2 temporary occlusion of blood vessel, w/ no lesions seen on MRI (Stroke 2009;40:2276)

Etiology: Atheroemboli from aortic arch cervical vessels (most common), cardioembolic thrombus (AF, CHF), small-vessel thrombosis (“lacunar” stroke); can also be 22 cervical vessel dissection, hypercoagulable state, hyperviscosity, paradoxical embolus through R

 

→ L shunt, endocarditis, infection (syphilis, CNS zoster), vasculitis Epidemiology: 2.7% of US adults report hx of stroke and 2.3% have hx of TIA; ↑ w/age: 8.3% of US adults ≥65 y report hx stroke; mean age at 1st stroke is 71–75 y; ↑ in African-American & Native American; major cause of mortality & disability

TIA is a “warning sign” for stroke; → 10–17% risk of stroke w/in 90 d, w/ half of events occurring w/in 2 d, if survive this period, 43% 10-y risk of MI, stroke, or vascular death

Risk factors: HTN, AF, tobacco use, dyslipidemia, physical inactivity, DM, CKD/ESRD

Evaluation (Stroke 2009;40:2276; Lancet Neurol 2005;4:727; Lancet 2007;369:283)

General approach: For pts w/new, current focal findings → ED; for pts reporting recent TIA sx, risk-stratify w/ABCD2 score to determine management

History: Acute onset of focal neurologic finding should prompt consideration of stroke; most commonly unilateral weakness or speech disturbance (dysarthria, aphasia), but can also present w/parasthesias, vertigo, ataxia, visual field defects

Exam: Complete, succinct neurologic exam: presence of facial hemiparesis (forehead spared – see “Bell’s palsy,” pronator drift, or abnormal speech → ⊕LR 5.5 for stroke)

All pts with suspected current TIA or stroke → ED STAT; document

“last seen well” time to help ED team determine if pt candidate for IV tPA (4.5 h from sx onset) or endovascular therapy (up to 24 h from sx onset)

Recent TIA symptoms: if red flags → ED, otherwise risk stratify (below)

Red flags: Suggest increased risk of stroke; PMHx: hypercoaguable state, prior stroke, hx Afib & not anticoagulated, mechanical valve; Sx: basilar TIA symptoms (vertigo/nausea, diplopia, tinnitus: up to 59% risk of subsequent stroke) → ED

Risk stratification: ABCD2 score (Age, BP, Clinical features of TIA, Duration of sx, DM) predicts short-term stroke risk; available at mdcalc.com/abcd2-score-for-tia/

 

Figure 9-5. Management algorithm for history of TIA-like symptoms

 

 

 

Labs: CBC, BMP, HbA1c, coags, lipids

Imaging: Should be of brain and cervical vessels; Brain: MRI w/diffusion-weighted imaging preferred (may be able to determine ischemia as well as infarction); CT acceptable; Cervical vessels: MRA, CT-A, or u/s; one approach is MRI/MRA of head & neck

Cardiac studies: to evaluate for cardioembolic etiology: ECG, rhythm strip, if no e/o carotid disease → Holter, TTE

Additional studies: If above unrevealing/per clinical suspicion, may consider endocarditis or hypercoagulability w/u, cardiac event monitor (Stroke 2004;35:1647)

Ischemic Stroke Treatment

Modifiable risk factors: BP control (in chronic setting), glycemic control, smoking cessation, moderation of EtOH, ↑ physical activity, wt loss (Stroke 2011;42:227)

Antiplatelet therapy: All TIA/ischemic stroke pts should be on antiplatelet tx unless already anticoagulated or contraindication; all regimens in table below acceptable; for recurrent TIA/stroke, no data to support changing regimen; ASA + warfarin ↑ bleeding risk w/o ↓ stroke risk (may be indicated in pts w/ CAD; see “CAD”) (Stroke 2011;42:227)

 

Agent	Advantages	Disadvantages
ASA 81 mg (or 325 mg if other indications, i.e., s/p MI)	Inexpensive, generally 1st line	GI s/e
ASA/dipyridamole 1 capsule	Slight (1%) risk reduction vs. ASA in 1 trial (Lancet 2006;367:1665)	Tolerance limited by HA, BID dosing
Clopidogrel 75 mg	No significant difference vs. ASA/dipyridamole (NEJM 2008;359:1238)	Higher cost

Dual antiplatelets: CHANCE trial demonstrated ↓ risk of recurrent stroke (8.2% vs. 11.7%) in pts w/ TIA/minor stroke & no cardioembolic source who were on 3 mo of dual anti-PLTs (ASA/clopidogrel) vs. ASA alone (NEJM 2013;369:11–19)

Anticoagulation: Indications listed in “special populations” below, refer to “Anticoagulation” chapter for selection of anticoagulant (warfarin vs. direct oral anticoagulants) & consideration of bridging; if concern for cerebral amyloid angiopathy (CAA, microhemorrhages on MRI) no anticoag 2/2 ↑ risk ICH

Lipid-lowering agents: SPARCL trial showed modest (↓ 2.2%) absolute risk reduction in recurrent ischemic stroke for high-dose atorvastatin vs. placebo (NEJM 2006;355:549); begin statin in all patients (Stroke 2014;45:2160)

SSRIs: FLAME trial showed ↑ motor recovery at 3 mo in stroke pts w/ mod–sev motor deficits, effect independent of hx depression (Lancet

Neurol 2011;10:123–30)

Complications: Assess for depression: Poststroke depression affects

~26% of pts; risk factors include prior social isolation, hx mood d/o, ↓ of independence after stroke; can be assoc w/ poor outcome (Stroke 1998;29:2311); fall risk (see “Fall Prevention”); aspiration risk (all pts w/ recent stroke should have had SLP eval, may need ongoing tx) Referrals: All pts w/ hx TIA or stroke should be seen by neurology; pts w/ recent stroke should be eval by multidisciplinary team including PT, OT, & SLP

Special Populations

Stroke due to atrial fibrillation: All pts should be anticoagulated unless contraindicated (Stroke 2011;42:227); due to risk of hemorrhagic transformation, most neurologists wait 1–4 wks poststroke to start

 

anticoag depending on stroke size and location, though no consensus; “bridging” w/ heparin not necessary (Arch Neurol 2008;65:1169) unless other indication (see “Atrial Fibrillation & Flutter”)

Stroke and cardiomyopathy: For pts w/ EF <35%, warfarin superior to ASA 325 in ↓ ischemic stroke risk but no benefit in composite outcome of death, ischemic stroke or ICH (WARCEF NEJM 2012;366:1859); ∴ in CHF pts w/ stroke hx, either warfarin or antiplatelets acceptable for 2° stroke prevention (Stroke 2011;42:227)

Stroke due to cervical artery dissection: Highest stroke risk in 1st few days

Extracranial → Tx w/ antiplatelet or anticoag × 3–6 mo (Stroke 2011;42:227); no data for superiority of anticoag vs. antiplatelet tx (tx practice varies) Intracranial → Due to SAH risk, anticoag generally avoided (NEJM 2001;344:898)

Carotid stenosis: (See “Carotid Disease”)

Intracranial stenosis: No data to support stenting; in pts w/ >70% intracranial stenosis, 30 d stroke risk ↑ w/ intracranial stenting vs. intensive med mgmt (SAMPRIS, NEJM 2011;265:993)

Patent foramen ovale: Common (15–25% of population), most studies with no significant benefit of PFO closure vs. med tx alone for 2° prevention (CLOSURE, I NEJM 2012;366:991; PC TRIAL, NEJM 2013;368:1083;

RESPECT, NEJM 2013;368:1092) 2 newer trials suggest ↓ risk of recurrent stroke in carefully selected pts (NNT 28 at 2 y, NNT 20 at 5 y) (Gore_REDUCE & CLOSE, NEJM 2017;377:1033 & 377:1011); Reasonable to start pts on antiplatelet agents (Stroke 2011;42:227); obtain LE U/S to r/o DVT (risk of paradoxical embolus) → start anticoag if ⊕ DVT