1000-2000 5 ьшò
.pdfCLINICALPEARLS
Thrombocytopenia is the most sensitive marker of increased portal pressure and large esophageal varices.
In acute bleeding, avoid β-blockers.
In acute bleeding, overtransfusion can elevate portal pressure and increase bleeding risk.
mebooksfree.com
ESSENTIALTREMOR SYNDROME
Jennifer E. Svarverud, DO 
Pamela R. Hughes, MD
BASICS
DESCRIPTION
Apostural (occurring with voluntary maintenance of a position against gravity) or kinetic (occurring during voluntary movement) flexion–extension tremor that is slow and rhythmic and primarily affects the hands and forearms, head, or voice with a frequency of 4 to 12 Hz
Older patients tend to have lower frequency tremors, whereas younger patients exhibit frequencies in the higher range.
May be familial, sporadic, or associated with other movement disorders
Incidence and prevalence increase with age, but symptom onset can occur at any age.
The tremor can be intermittent and exacerbated by emotional or physical stressors, fatigue, and caffeine.
System(s) affected include neurologic, musculoskeletal, ear/nose/throat (ENT) (voice)
EPIDEMIOLOGY
Essential tremor is the most common pathologic tremor in humans.
Incidence
Can occur at any age but bimodal peaks exist in the 2nd and 6th decades
Incidence rises significantly after age 49 years.
Prevalence
The overall prevalence for essential tremor has been estimated between 0.4% and 0.9% but is increased in older patients with an estimated 4.6% at age 65 years and up to 22% at age 95 years.
ETIOLOGYAND PATHOPHYSIOLOGY
Suspected to originate from an abnormal oscillation within thalamocortical and cerebello-olivary loops, as lesions in these areas tend to reduce essential tremor
mebooksfree.com
Essential tremor is not a homogenous disorder; many patients have other motor manifestations and nonmotor features, including cognitive and psychiatric symptoms.
Genetics
Positive family history in 50–70% of patients; autosomal dominant inheritance is demonstrated in many families with poor penetrance. Twin studies suggest that environmental factors are also involved.
Alink to genetic loci exists on chromosomes 2p22–2p25, 3q13, and 6p23. In addition, a Ser9Gly variant in the dopamine D3 receptor gene on 3q13 has
been suggested as a risk factor.
COMMONLYASSOCIATED CONDITIONS
Can be present in 10% of patients with Parkinson disease (PD); characteristics of PD that distinguish it from essential tremor include 3- to 5-Hz resting tremor; accompanying rigidity, bradykinesia, or postural instability; and no change with alcohol consumption
Patients with essential tremor have a 4% risk of developing PD.
Resting tremor, typically of the arm, may be seen in up to 20–30% of patients with essential tremor. Although action tremor is the hallmark feature of essential tremor, it is commonly found in patients with PD as well.
DIAGNOSIS
HISTORY
Core criteria for diagnosis
–Bilateral (less likely unilateral) action (postural or kinetic) tremor of the hands and forearms that is most commonly asymmetric
–Absence of other neurologic signs, with the exception of cogwheel phenomenon
–May have isolated head tremor with no signs of dystonia
Secondary criteria include long duration (>3 years), positive family history, and beneficial response to alcohol.
PHYSICALEXAM
Tremor can affect upper limbs (~95% of patients).
Less commonly, the tremor affects head (~34%), lower limbs (~30%), voice
mebooksfree.com
(~12%), tongue (~7%), face (~5%), and trunk (~5%).
DIFFERENTIALDIAGNOSIS
PD
Wilson disease
Hyperthyroidism
Multiple sclerosis
Dystonic tremor
Cerebellar tremor
Asterixis
Psychogenic tremor
Orthostatic tremor
Drug-induced or enhanced physiologic tremor (amiodarone, cimetidine, lamotrigine, itraconazole, valproic acid, SSRIs, steroids, lithium, cyclosporine, β-adrenergic agonists, ephedrine, theophylline, tricyclic antidepressants [TCAs], antipsychotics)
DIAGNOSTIC TESTS & INTERPRETATION
Initial Tests (lab, imaging)
No specific biologic marker or diagnostic test is available.
Ceruloplasmin and serum copper to rule out Wilson disease
Thyroid-stimulating hormone to rule out thyroid dysfunction
Serum electrolytes, BUN, creatinine
Brain MRI usually is not necessary or indicated unless Wilson disease is found or exam findings imply central lesion.
Diagnostic Procedures/Other
Accelerometry evaluates tremor frequency and amplitude; >95% of PD cases exhibit frequencies in the 4- to 6-Hz range, and 95% of essential tremor cases exhibit frequencies in the 5- to 8-Hz range.
Surface electromyography is less helpful in distinguishing essential tremor from PD.
Test Interpretation
Posture-related tremor seen on exam
mebooksfree.com
TREATMENT
MEDICATION
Pharmacologic treatment should be considered when tremor interferes with activities of daily living (ADLs) or causes psychological distress.
First Line
Propranolol 60 to 320 mg/day in divided doses or in long-acting formulation reduces limb tremor magnitude by ~50%, and almost 70% of patients experience improvement in clinical rating scales. There is insufficient evidence to recommend propranolol for vocal tremor. Single doses of propranolol, taken before social situations that are likely to exacerbate tremor, are useful for some patients.
Primidone 25 mg at bedtime, gradually titrated to 150 to 300 mg at bedtime, improves tremor amplitude by 40–50%. Maximum dose is 750 mg/day, with doses >250 mg/day typically divided to BID or TID. Low-dose therapy (<250 mg/day) is just as effective as high-dose (750 mg/day) therapy.
Propranolol and primidone have similar efficacy when used as initial therapy for limb tremor; both carry a level Arecommendation (1)[A].
30–50% of patients will not respond to either propranolol or primidone.
Second Line
Topiramate at a mean dose of 292 mg/day demonstrated significantly greater reduction in Tremor Rating Scale (TRS) compared with placebo (7.70 vs. 0.08; p < .005; baseline TRS = 37.0) in a small study combining results of three double-blind, randomized, controlled trials following a common protocol. Use is limited by dropout rates as high as 40% due to appetite suppression, weight loss, paresthesias, and concentration difficulties (2)[B].
Gabapentin up to 400 mg TID (3)[B]
Sotalol, nadolol, and atenolol are alternative β-blockers; each has less evidence than propranolol to support use.
Clonazepam and alprazolam should be used with caution because of potential abuse.
Clozapine has shown efficacy at doses of 6 to 75 mg/day but is recommended only for refractory cases of limb tremor because of a 1% risk of agranulocytosis. The American Academy of Neurology (AAN) indicates that insufficient evidence exists to support or refute the efficacy of clozapine for chronic use (1)[A].
mebooksfree.com
Memantine, in a pilot study using doses up to 40 mg/day, showed significant benefit in a small subset of the study group. Adverse events at this dose included dizziness, somnolence, and poor energy (4)[B].
Pramipexole, at a dose of 2.1 mg/day, demonstrated moderate efficacy in reducing severity of tremor in a pilot study of 29 patients. Immediateand extended-release formulations were equally effective (5)[B].
Levetiracetam and 3,4-diaminopyridine are probably ineffective at reducing limb tremor and should not be considered according to the AAN (1)[A].
Other medications that have been evaluated for treatment of essential tremor, with limited data to support their use, include acetazolamide, clonidine, flunarizine, methazolamide, nimodipine, olanzapine, phenobarbital, pregabalin, quetiapine, sodium oxybate, and zonisamide (1)[A].
Alcohol may provide transient improvement in symptoms, but its brief duration of action, subsequent rebound, and associated risk of developing alcohol addiction make it a less attractive option for longer term treatment. Alcohol may be an appropriate option for short-term, situation-specific improvement in symptoms.
Botulinum toxin Ainjections should be offered as a treatment option for cervical dystonia (level Arecommendation from AAN) and may be offered for blepharospasm, focal upper extremity dystonia, adductor laryngeal dystonia, and upper extremity essential tremor. Limited data support its use for head and vocal tremor (6)[B].
ISSUES FOR REFERRAL
Referral to a neurologist can help to differentiate those with dystonia, neuropathic tremor, PD, or drug-induced tremor.
SURGERY/OTHER PROCEDURES
Deep brain stimulation provides a magnitude of benefit that is superior to all available medications and may be used to treat medically refractory limb tremor; it has fewer adverse effects than thalamotomy.
Bilateral thalamic stimulation is effective in reducing tremor and functional disability; however, dysarthria is a possible complication.
Unilateral thalamotomy may be used to treat limb tremor that is refractory to medical management.
Bilateral thalamotomy is not recommended because of adverse side effects.
mebooksfree.com
ONGOING CARE
DIET
Avoid caffeine.
PATIENT EDUCATION
Although essential tremor can cause significant impairment in daily functioning, it does not decrease life expectancy.
PROGNOSIS
Tremor tends to worsen with age, increasing in amplitude.
REFERENCES
1.Zesiewicz TA, Elble RJ, Louis ED, et al. Evidence-based guideline update: treatment of essential tremor: report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2011;77(19):1752–1755.
2.Connor GS, Edwards K, Tarsy D. Topiramate in essential tremor: findings from double-blind, placebo-controlled, crossover trials. Clin Neuropharmacol. 2008;31(2):97–103.
3.Gironell A, Kulisevsky J, Barbanoj M, et al. Arandomized placebocontrolled comparative trial of gabapentin and propranolol in essential tremor. Arch Neurol. 1999;56(4):475–480.
4.Handforth A, Bordelon Y, Frucht SJ, et al. Apilot efficacy and tolerability trial of memantine for essential tremor. Clin Neuropharmacol. 2010;33(5):223–226.
5.Herceg M, Nagy F, Pál E, et al. Pramipexole may be an effective treatment option in essential tremor. Clin Neuropharmacol. 2012;35(2):73–76.
6.Simpson DM, Blitzer A, Brashear A, et al; for Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Assessment: botulinum neurotoxin for the treatment of movement disorders (an evidence-based review): report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology. 2008;70(19):1699–1706.
ADDITIONALREADING
Bain P, Brin M, Deuschl G, et al. Criteria for the diagnosis of essential tremor.
mebooksfree.com
Neurology. 2000;54(11 Suppl 4):S7.
Buijink AW, Contarino MF, Koelman JH, et al. How to tackle tremor— systematic review of the literature and diagnostic work-up. Front Neurol. 2012;3:146.
Deuschl G, Raethjen J, Hellriegel H, et al. Treatment of patients with essential tremor. Lancet Neurol. 2011;10(2):148–161.
Elias WJ, Shah BB. Tremor. JAMA. 2014;311(9):948–954.
Flora ED, Perera CL, Cameron AL, et al. Deep brain stimulation for essential tremor: a systematic review. Mov Disord. 2010;25(11):1550–1559.
Schuurman PR, Bosch DA, Bossuyt PM, et al. Acomparison of continuous thalamic stimulation and thalamotomy for suppression of severe tremor. N Engl J Med. 2000;342(7):461–468.
Sullivan KL, Hauser RA, Zesiewicz TA. Essential tremor. Epidemiology, diagnosis, and treatment. Neurologist. 2004;10(5):250–258.
Thenganatt MA, Louis ED. Distinguishing essential tremor from Parkinson’s disease: bedside tests and laboratory evaluations. Expert Rev Neurother. 2012;12(6):687–696.
Zeuner KE, Deuschl G. An update on tremors. Curr Opin Neurol. 2012;25(4):475–482.
CODES
ICD10
G25.0 Essential tremor
CLINICALPEARLS
Core criteria for diagnosis of essential tremor include bilateral action or postural tremor of the hands, forearm, and/or head without a resting component.
Beneficial response to alcohol and positive family history help to differentiate essential tremor from PD (PD is characterized by tremor at rest, bradykinesia, and rigidity, and it does not improve with alcohol use.).
10% of patients with PD will have both resting tremors of PD and essential tremor.
Wilson disease, thyroid disease, and medication effect should be ruled out. 
Brain MRI is usually not necessary or indicated.
mebooksfree.com
First-line treatments include propranolol and primidone. 30–50% of patients will not benefit from these first-line treatments.
mebooksfree.com
EUSTACHIAN TUBE DYSFUNCTION
Adam W. Kowalski, MD 
Vernon Wheeler, MD, FAAFP
BASICS
DESCRIPTION
Aspectrum of disorders involving impairment of the functional valve of the eustachian tube (ET)
ETD can be classified as patulous dysfunction, in which the ET is excessively open, or dilatory dysfunction, in which there is failure of the tubes to dilate (i.e., open) appropriately.
Pathophysiology related to pressure dysregulation, impaired protection secondary to reflux of irritating material into the middle ear, or impaired clearance by the mucociliary system
May occur in the setting of pressure changes (e.g., scuba diving or air travel) or acute upper airway inflammation (e.g., allergic or infectious rhinosinusitis, acute otitis media [OM])
Chronic ETD may lead to a retracted tympanic membrane, recurrent serous effusion, recurrent OM, adhesive OM, chronic mastoiditis, or cholesteatoma.
System(s) affected: auditory
Synonym(s): auditory tube dysfunction; ET disorder; blocked ET; patulous ET
ALERT
Sudden sensorineural hearing loss (SSNHL) can be misdiagnosed as ETD.
Asimple 512-Hz tuning fork test lateralizes to the opposite ear in SSNHL and to the affected ear in ETD with conductive hearing loss.
Any SSNHLis a medical emergency and should be referred to an otolaryngologist immediately.
EPIDEMIOLOGY
Most common in children <5 years of age, thought to be related to anatomical differences (see “Etiology and Pathophysiology” section)
Usually decreases with age
Incidence
70% of children by age 7 years have experienced ETD.
mebooksfree.com