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Appendix

 

 

 

Table 71 Metabolic myopathies (p. 340) (continued)

 

 

 

 

 

Myopathy/Gene Locus

Defect/Inheritance

Features

 

 

 

 

 

Mitochondria

 

 

 

 

!

CPEO3

! mtDNA deletion in ca. 50% of

!

Ptosis, external ophthalmople-

 

 

 

cases

 

gia, tapetoretinal degenera-

 

 

 

 

 

tion, cardiac arrhythmias, pro-

!

 

 

 

 

ximal myopathy

KSS4

!

mtDNA deletion/

! Onset before 13th year of life,

 

 

!

duplication

 

ataxia, hearing impairment,

 

 

 

 

 

CSF protein, endocrine distur-

 

 

 

 

 

bances, otherwise identical to

!

MERRF5

!

 

!

CPEO

mtDNA point mutation

Myoclonus, ataxia, seizures

!

MELAS6

!

mtDNA point mutation

!

Episodic vomiting, focal

 

 

 

 

 

seizures, dwarfism, proximal

!

 

 

 

 

muscle weakness

LHON7

!

mtDNA point mutation

! Acute/subacute bilateral loss of

!

MILS8

!

 

!

vision, eye pain

mtDNA point mutation9

Developmental delay, ataxia,

 

 

 

 

 

dystonia, visual disturbances,

 

 

 

 

 

respiratory disturbances10

1 Adult type. 2 Carnitine palmitoyl transferase; defect located on outer mitochondrial membrane in type I, and on inner membrane in type II. 3 Chronic progressive external ophthalmoplegia. 4 Kearns–Sayre syndrome; cardiac pacemaker implantation may be necessary in patients with cardiac arrhythmias. 5 Myoclonus epilepsy with ragged red fibers. 6 Myopathy, encephalopathy, lactic acidosis, and “strokelike episodes”. 7 Hereditary hepaticoptic neuropathy. 8 Maternally inherited Leigh syndrome. 9 Autosomal recessive and sporadic forms are also found. 10 T2-weighted MRI reveals bilateral symmetric lesions (brain stem, periaqueductal region, cerebellum, basal ganglia)

Table 72 Drugs that can aggravate myasthenia gravis (p. 342)

Drugs That Can Aggravate Myasthenia Gravis

Alternatives

 

 

Antibiotics: tetracyclines, aminoglycosides, polymy-

Cephalosporins, chloramphenicol

xins, gyrase inhibitors, penicillins

 

Psychoactive drugs: benzodiazepines, barbiturates,

Promethazine, thioridazine. Chlordiazepoxide, ma-

tricyclic antidepressants, chlorpromazine,

protiline, mianserin or carbamazepine can be used at

haloperidol, droperidol, lithium

low doses and with careful monitoring

Anticonvulsants: phenytoin, ethosuximide, barbitu-

Carbamazepine

rates

 

Cardiovascular agents: Quinidine, ajmaline, procain-

Digitalis, reserpine, methyldopa, tocainide, verapamil

amide, lidocaine, ganglioplegics, nifedipine, !-block-

(low-dose)

ers1

 

Miscellaneous: ACTH, corticosteroids2, D-penicil-

Aspirin, gold, indometacin, acetaminophen, di-

lamine, morphine and derivatives, magnesium,

clofenac, local/regional anesthesia, spinal anesthesia,

general anesthesia (muscle relaxants)

inhalant anesthetics/deeper general anesthesia

 

(Selected drugs from McNamara and Guay, 1997)

1 Mask symptoms of myasthenia. 2 High starting dose.

 

Appendix

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Appendix

Appendix

Table 73 Myasthenia-related crises (p. 342)

Syndrome

Symptoms and Signs

Precipitating Factors

 

 

 

Myasthenic crisis

Restlessness, anxiety, confusion, respira-

Infectious diseases, surgical interventions,

 

tory weakness, weak cough, dysphagia,

anesthesia, drugs, psychosocial stress, im-

 

dysarthria, mydriasis, ptosis, tachycardia,

paired drug uptake (vomiting, diarrhea),

 

pallor

disease progression, previously unde-

 

 

tected myasthenia (and previously men-

 

 

tioned factors)

Cholinergic crisis

Restless, anxiety, confusion, respiratory

Overdosage (relative) of AChE inhibitors;

 

weakness, weak cough, dysphagia, dy-

acetylcholine poisoning

 

sarthria, miosis, bradycardia, skin redden-

 

 

ing, muscle fasciculation/spasms, saliva-

 

 

tion, tenesmus, diarrhea

 

 

 

 

Table 74 Ancillary tests in myasthenia gravis (p. 342)

Test

Objective

Interpretation of Results

 

 

 

Edrophonium chloride test1 (Ten-

Increase in muscle strength (with

Marked improvement (beginning

silon, Camsilon)

improvement of ptosis, eye move-

30 seconds after administration

 

ments, speech, and swallowing)

and lasting roughly 5 minutes)

 

 

unequivocal response. Sensitivity

 

 

for OMG2: ca. 86%, for GMG3: ca.

 

 

95%

Electromyography (EMG)4

Documentation of impaired neu-

A decrement of 10% or more is

 

romuscular conduction (decre-

pathological. Sensitivity of serial

 

ment in amplitude seen with se-

stimulation in OMG: ca. 34%; in

 

rial stimulation; jitter may be ob-

GMG: up to 77%. Prior muscle ex-

 

served in single-fiber EMG)

ercise more pronounced decre-

 

 

ment. Sensitivity of single-fiber

 

 

EMG: ca. 92%

Serum acetylcholine receptor anti-

Documentation of presence of

Sensitivity: 50% in OMG, ca. 90%

body titer

acetylcholine receptor antibodies

in GMG. False-positive results may

 

 

occur in Lambert–Eaton syn-

 

 

drome, rarely in amyotrophic

 

 

lateral sclerosis

Diagnostic imaging5

Measurement of thymus

Thymic enlargement due to thy-

 

 

moma or hyperplasia

 

 

(Phillips and Melnick, 1990)

1 Short-term inhibition of cholinesterase, given intravenously for diagnostic purposes. 2 Ocular myasthenia gravis. 3 Generalized myasthenia gravis. 4 Example: Repeated stimulation of accessory nerve (3/sec for 3 seconds) and recording of activity in trapezius muscle. 5 CT (contrast-enhanced) or MRI (younger patients, better differentiation of thymic hyperplasia).

404

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Appendix

Table 75 Toxic myopathies (p. 347)

Syndrome

Substances (selected)

 

 

Muscle weakness with or without pain; rhabdomyolysis may occur

Alcohol, chloroquine, cimetidine, clofibrate, cocaine, colchicine, ciclosporin, disulfiram, emetine, ergotamine, gemfibrozil, induced hypokalemia (diuretics, licorice), imipramine, isoniazide, lithium, lovastatin, meprobamate, niacin, pentazocine, thyroid hormones, vincristine, zidovudine

Myalgia

Alcohol, allopurinol, cimetidine, clofibrate, clonidine,

 

dihydroergotamine, ergotamine, methyldopa, suc-

 

cinylcholine, vincristine, zidovudine

Polymyositis, pseudo-lupus erythematosus

Bezafibrate, chlorpromazine, cimetidine, clofibrate,

 

D-penicillamine, etofibrate, etofyllin clofibrate, fenofi-

 

brate, gold, hydralazine, isoniazide, L-tryptophan,

 

penicillin, phenytoin, procainamide, tetracyclines,

 

zidovudine

Myotonia

Ciclosporin, 20,25-diazocholesterol, diuretics, D-peni-

 

cillamine, fenoterol, pindolol, propranolol

Local muscle lesions (pain, swelling, local muscular

Heroin, insulin, meperidine, pentazocine

atrophy)

 

Appendix

405

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Appendix

Appendix

Table 76 Neuromuscular paraneoplastic syndromes (pp. 347, 388)

Site of Lesion

Syndrome

Symptoms and

Common

Lesions/

 

Manifestation

Signs

Tumors

Antibodies

 

 

 

 

 

Motor neuron

Subacute muscular

Asymmetrical para-

Small-cell lung

Motor neurons/

 

atrophy (hands,

lysis, muscle atro-

cancer, lymphoma,

Anti-Hu1

 

bulbar muscles)

phy (p. 304)

renal cell carci-

 

 

 

weeks to months

 

 

noma

 

 

Spinal posterior

Subacute sensory

Marked sensory

Small-cell lung

Spinal ganglia

root, ganglion

neuronopathy

loss, areflexia,

cancer, other lung

 

 

 

weeks to months

ataxia, paresthe-

tumors

 

 

 

 

 

siae, pain

 

 

 

 

Proximal peripheral

!

Acute poly-

!

Ascending sen-

!

Hodgkin disease

Segmental demy-

nerve

 

radiculopathy

 

sorimotor defi-

 

 

elination, neuritis

 

!

hours to days

!

cits2

!

 

 

 

 

Chronic poly-

Chronic pro-

Small-cell lung

 

 

 

 

radiculopathy3

 

gressive/recur-

 

cancer, lym-

 

 

 

 

weeks to

 

rent sensorimo-

 

phoma, my-

 

 

 

 

months

 

tor deficits

 

eloma

 

 

Distal peripheral

!

Paraproteinemic

!

See p. 328

!

Plasmacytoma

!

Segmental de-

nerve

 

polyneuropathy

 

 

 

 

 

myelination

 

 

weeks to

 

 

 

 

 

 

 

!

months

!

Distal sym-

!

Small-cell lung

!

Mainly axonal

 

Sensorimotor

 

 

polyneuropathy

 

metrical poly-

 

cancer, other

 

lesions

 

 

weeks to

 

neuropathy

 

cancers

 

 

 

!

months

!

 

!

 

!

 

 

Neuromyotonia

Muscle stiff-

Thymoma, lung

Distal motor

 

 

 

 

ness, cramps

 

cancer

 

nerve/Anti-

 

 

 

 

 

 

 

 

VGPC4

End-plate region

!

Lambert–Eaton

!

See p. 342

!

Small-cell lung

!

See p. 343/

 

 

syndrome

 

 

 

cancer; breast,

 

Anti-VGCC anti-

 

 

weeks to

 

 

 

prostate or

 

bodies5

 

!

months

!

 

!

stomach cancer

!

 

 

Myasthenia

See p. 342

Thymoma

See p. 343/

 

 

gravis weeks

 

 

 

 

 

Skeletal muscle

 

 

to months

 

 

 

 

 

antibodies

Skeletal muscle

!

Polymyositis/

!

See p. 344

!

Various cancers

!

Myonecrosis,

 

 

dermatomyosi-

 

 

 

(breast, lung or

 

lymphomono-

 

 

tis months to

 

 

 

ovarian cancer,

 

cytic infiltrates

 

!

years

!

 

!

lymphoma)

!

 

 

Rhabdomyolysis

Rapidly progres-

Various cancers

Myonecrosis,

 

 

days to

 

sive paralysis,

 

 

 

rare inflam-

 

 

weeks

 

dysphagia

 

 

 

matory infil-

 

 

 

 

 

 

 

 

trates

 

 

 

 

 

 

 

 

 

(Brown, 1998)

1 In small-cell lung cancer. 2 Similar to Guillain–Barré syndrome (p. 326). 3 Similar to CIDP (p. 328). 4 VGPC = voltage-gated potassium channel; EMG shows high-frequency discharges (150–300 Hz). 5 VGCC = voltage-gated calcium channel.

406

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Appendix

 

 

 

 

Table 77 Laboratory tests (p. 351)

 

 

 

 

 

 

Test/Objective

Risks

Comments

 

 

 

 

Antiepileptic drugs

 

 

 

!

Verify drug compliance

!

Laboratory error

Time of sample collection is deter-

! Assess for drug resistance

!

Misuse of measured values

mined by the pharmacokinetics of

! Avoid underdosage or over-

 

(the physician should be

the antiepileptic drug in question

!

dosage

 

guided by the clinical objective

 

Assess for drug interactions

 

of a seizure-free state, rather

 

 

 

 

than by “therapeutic levels”)

 

Lumbar puncture

 

 

 

!

Measure CSF pressure

!

Increased intracranial pressure3

Suboccipital or lateral cervical

! Obtain CSF sample for analysis

!

Intraspinal mass4

puncture is very rarely indicated

!

Intrathecal drug administration

!

Postpuncture headache

(e. g. if a CSF sample is required,

!

Diagnosis (contrast agent1,

!

Intraspinal hemorrhage

but cannot be obtained by lumbar

 

radioactive substances2)

!

(coagulopathy)

puncture, or for myelography

 

 

Meningitis

above a spinal lesion). Myelogra-

 

 

!

Discitis

phy and MRI have rendered

 

 

 

 

Queckenstedt’s test5 obsolete

1 For myelography. 2 For scintigraphy. 3 Risk of transtentorial/cerebellar herniation. 4 Risk of acute spinal decompensation with paraplegia. 5 Compression of jugular vein to test for patency of subarachnoid space, which may be blocked, for example, by a spinal tumor.

Appendix

407

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