A. Types of Problems

1. Pain
2. Spasm
3. Cramps
4. Weakness

B. Spasms

1. Brief, unsustained contraction of single or multiple muscles
2. From abnormal electrical activity (CNS, motor neuron), or within muscle fiber
3. CNS etiology usually affects entire groups of muscle
   1. Entire limb, group muscles, side of body
   2. Rhythmic or intermittant
   3. May be frank seizures (as compared with clonus)
4. Peripheral lesions usually cause random muscle movements
5. Segmental myoclonus
   1. Focal disease within brainstem or spinal cord
   2. Abnormal motor neurron firing
   3. Local vascular disease, tumor, etc. may be cause
6. Facial Movements
   1. Hemifacial Spasm - paroxysmal facial nerve activity; MRI needed for workup
   2. Tics - voluntary and hereditary forms such as Tourette Syndrome
   3. Acute unilateral facial weakness - usually due to stroke or Bell's palsy [1]
   4. Synkinesias - aberrant regeneration of facial nerve usually due to Bell's palsy
   5. Trigeminal Neuralgia
   6. Facial Myokymia
7. Trigeminal Neuralgia (tic doloureux)
   1. Brief paroxysmal lancinating pain
   2. Unilateral
   3. Pain causes involuntary contraction of facial muscles
   4. Carbamazepine is most effective medical therapy
   5. Microvascular decompression is effective and well tolerated [4]
8. Facial Myokymia
   1. Continuous twitching of facial muscles
   2. Usually from multiple sclerosis or pons tumor
   3. Amyotrophic Lateral Sclerosis
   4. Anterior horn or peripheral nerve
9. Abnormal Limb Movements
   1. Fasciculations usually found - spontaneous firing of entire motor unit
   2. Usually not pathological unless weakness also occurs
   3. Seizures (gran mal or myoclonic)
   4. Akathesia - motor restlessness seen with basal ganglion lesions
   5. Akathesia often seen in idiopathic Parkinsonism and with Neuroleptic therapy
   6. Restless Leg Syndrome (see below)
10. Fibromyalgia
    1. Specific tender points in muscles / fibrous tissue
    2. Usually accompanied by a sleeping disorder
11. Evaluation
    1. EMG / Nerve Conduction Studies usually best
    2. Underlying electrolyte disorders may affect symptoms (especially K+, Mg2+, Ca2+, PO4)
    3. Consider EEG if CNS lesion suspected
    4. MRI may also be helpful
12. Muscle Relaxants (Analgesics)
    1. Most act centrally on cholinergic or GABAnergic neurons, cause sedation
    2. Baclofen (GABA analog): initial 5mg po tid x 3 ays, up to 40-80mg/d (20mg qid)
    3. Dantrolene (Dantrium®): for upper motor neuron disorders, initial 25mg po x 7 days, then 25mg tid x 7 days, then 50mg tid x 7 days, then 100mg tid max
    4. Cyclobenzaprine (Flexeril®): 5-10mg tid initial to max 20mg tid
    5. Orphenadrine (Norlfex®): central relaxant, 100mg bid; injection 60mg IV/IM q12 hours
    6. Chlorzoxazone (Parafon Forte®): 500mg tid-qid, up to 750mg tid-qid
    7. Methocarbamol (Robaxin®): initial 1500mg qid for 2-3 days, then reduce to tid
    8. Metaxolone (Skelaxin®): 800mg po tid-qid
    9. Carisoprodol (Soma®): 350mg tid and hs
    10. Tizanidine (Zanaflex®): central alpha2-adrenergic agonist, initial 4mg q6-8 hours, may increase to 8mg po tid-qid
    11. Diazepam (Valium®): benzodiazepine, 2-10mg po tid - qid

C. Restless Leg Syndrome [2,5]

1. Diagnostic Features
   1. Uncomfortable sensation in legs and thighs at rest (akathisia)
   2. Relieved by movement - walking or moving legs
   3. Brought on by rest (sitting or lying odwn)
   4. Worse at night or in evening
   5. Often with involuntary leg movements while patient is asleep or awake
2. Common in middle aged women
   1. Affects 2-5% of population overall
   2. Affects up to 20% of women during pregnancy
   3. Common in uremia, neuropathies, diabetes, sleep myoclonus, arthritis
   4. Increased incidence of iron deficiency in patients with RLS
   5. Iron parameters should be evaluated in all patients with RLS
3. Often more prominant at night, when leg cramping may complicate problem
   1. Over 80% of patients have flexion movements of legs during non-REM sleep
   2. May lead to sleep disturbance
   3. Difficult to distinguish from leg cramping
4. Treatment
   1. Enhancement of dopamine pathways is often effective, particularly for nighly symptoms
   2. Levodopa or Sinamet® are probably first line (low cost, good efficacy)
   3. Pergolide 0.05mg po qd initially (up to 0.75mg qd) reduces movements and improves sleep [6]
   4. Caution with withdrawal of dopamine and its agonists - slow reductions required
   5. Frequent episodes also respond to sedative hypnotics
   6. These include zolpidem (Ambien®), zaleplon (Sonata®) and benzodiazepines
   7. Benzodiazepines include oxazepaqm (Serax®), triazolam, clonazepam (Klonopin®)
   8. Other treatments include gabapentin, valproate, opiates
   9. Gabapentin 600-2400mg daily (divided) reduces sensory and motor symptoms of RLS [3]
   10. Quinine 300mg po qhs had definite benefit in meta-analysis; may require >4 weeks
   11. Quinine should not be used in patients with G6PD deficiency (see below)
5. RLS Foundation: www.rls.org

D. Sustained Muscle Contractions

1. Central Nervous System (CNS) Etiology
   1. Tone increased with contraction - usually implies CNS dysfunction
   2. Usually due to loss of inhibititory neurons in CNS
   3. Spasticity, rigidity, and tonus may occur
   4. Disease of basal ganglia leading to dystonia
   5. Botulinum Toxin A (Botox) of benefit in post-stroke hand and wrist spasticity [9]
2. Peripheral Etiology
   1. Repetitive depolarization of motor unit
   2. Motor neuron dysfunction
   3. Neuromuscular junction abnormalities
   4. Muscle fiber disease
3. Cramp
   1. Painful, involuntary contraciton of muscles
   2. Usually with high frequency rates
   3. EMG may show ~300 contractions per second
   4. May lead to fiber necrosis with creatinine kinase leakage (serum elevation)
   5. Generalized cramps, motor nerve disease: consider amyotrophic lateral sclerosis (ALS)
   6. Differential Diagnosis: tetanus, stiff man syndrome
4. Myotonia (muscle stiffness)
   1. Muscle contraction with decreased relaxation
   2. Myotonic dystrophy - usually worse with cold
   3. Paradoxical myotonia -usually worsens with repeated activity
5. Dystonia [10,11]
   1. Disorder causing variable muslce tone and recurrent muscle spasm
   2. Movement disorder causing sustained muscle contractions, repetitive twisting movements, and abnormal postures of trunk, neck face, or arms and legs
   3. Results from involvuntary concomitant contraction of agonist and antagonist muscles, with overflow of unwanted muslce contractions into adjacent muscles
   4. Movements may be either slow or rapid, and can change during different activities or postures, and may become fixed in advanced cases

E. Leg Cramps

1. Characteristics
   1. Unclear etiology
   2. Exercise / Stretching may improve symptoms
   3. Often occur at night
   4. Frequent in dialysis patients
   5. May be difficult to distinguish from restless leg syndrome (see above)
2. Treatment
   1. Treat with Quinine ± verapamil
   2. Quinine 300mg po qhs effective in crossover study and meta-analysis
   3. Check G6PD levels; do not use quinine with low levels of G6PD, it can cause hemolysis
   4. Cinchonism (tinnitus, poor hearing, blurred vision, nausea) - major side effect of quinine
   5. Quinine also causes microangiopathic hemolytic anemia (monitor platelets) [7]
   6. Vitamin E was not effective
   7. Smoking decreases efficacy of quinine
   8. In quinine failures, consider use of orphenadrine (Norflex®) 100mg po bid or qhs.
   9. Clonazepam (Klonopin®) is also effective for nocturnal cramping

E. Myalgias

1. Trauma - usually focal. May have creatinine kinase elevation
2. Fibromyalgia
   1. Also called fibrositis or fibromyositis
   2. Trigger points characteristic
   3. Typically 20-35 year old women
   4. Painful swellings without fluid accumulation
   5. Fatigue, insomnia, depression common
   6. No changes in serum muscle enzymes; no laboratory abnormalities
3. Polymyalgia Rheumatica
   1. Patients usually >50 years old
   2. High ESR in majority
   3. Stiffness and pain in shoulder and hip musculature
   4. Actually localizes more to joints (syndrome is actually an arthralgia)
   5. Low dose glucocorticoids are far more effective than non-steroidal agents (NSAIDs)
4. Other Rheumatologic Conditions
   1. Polymyositis and Dermatomyositis may be painless but fatigue is prominant
   2. Glucocorticoid induced myopathy should be considered (usually painless also)
   3. Drug induced myopathies are also fairly common

F. Weakness

1. Inflammatory Muscle Conditions
   1. Dermatomyositis and Polymyositis
   2. Overlap Syndromes - often with lupus or scleroderma (systemic sclerosis)
   3. Inclusion Body Myositis
2. Electrolyte Disorders
   1. Hypokalemia > Hyperkalemia
   2. Hypocalcemia (tetany)
   3. Hypercalcemia
   4. Hypophosphatemia
   5. Hyponatremia
   6. Hypomagnesemia
3. Neuromuscular Junction Diseases
   1. Myasthenia Gravis
   2. Eaton-Lambert Syndrome
4. Demyelinating Conditions
   1. Multiple Sclerosis (CNS)
   2. Guillian-Barre Syndrome
   3. Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)
5. Muscle Atrophy [8]

References

1. Gilden DH. 2004. NEJM. 351(13):1323
2. O'Keeffe ST. 1996. Arch Intern Med. 156(3):243
3. Garcia-Borreguero D, Larrosa O, de la Llave Y, et al. 2002. Neurology. 59:1573
4. Barker FG II, Jannetta PJ, Bissonette DJ, et al. 1996. NEJM. 334(17):1077
5. Earley CJ. 2003. NEJM. 348(21):2103
6. Wetter TC, Stiasny K, Winkelmann J, et al. 1999. Neurology. 52:944
7. Kojouri K, Vesely SK, George JN. 2002. Ann Intern Med. 135(12):1047
8. Emery AEH. 2002. Lancet. 359(9307):687
9. Brashear A, Gordon MF, Elovic E, et al. 2002. NEJM. 347(6):395
10. Tarsy D and Simon DK. 2006. NEJM. 355(8):818
11. Greene P. 2005. NEJM. 352(5):498