EM guidemaps - Neuromuscular weakness

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Introduction

General principles

Clinical decision-making in an ED setting Appendix
Introduction

- this guidemap is primarily focused on problem-solving neuromuscular disorders causing rapidly progressive weakness that will cause the patient to present to an ED with a history of acute weakness, and it does not discuss neuromuscular diseases causing chronic, slowly progressive weakness

- neuromuscular weakness can be due to UMN or LMN diseases, neuromuscular junction disorders, or muscle diseases; this guidemap mainly offers a conceptual approach to neuromuscular weakness so that an emergency physician can narrow the differential diagnoses to a likely set of possible diagnoses - on the basis of fundamental pathophysiological principles (myopathy vs neuropathy vs neuromuscular transmission disorder vs motor neuron)

- this guidemap is linked to the myopathy and myoglobinuria sub-guidemap, which provides more problem-solving information on myopathies and myoglobinuria
 
General principles

- the symptom of "weakness" is a common, and often vague, complaint and an emergency physician must first differentiate true neuromuscular weakness from diseases that can produce non-specific weakness and/or fatigue eg. anemia, acute blood loss, cardiopulmonary diseases causing hypoxia, single or multiple end organ failure (heart failure, renal failure, hepatic failure), metabolic imbalance, endocrine dysfunction, connective tissue diseases, fibromyalgia, chronic fatigue syndrome, and psychological disorders

- the most useful clues suggesting true neuromuscular weakness come from a targeted history that specifically inquires about particular muscular activities that the patient cannot easily accomplish

- difficulty climbing stairs, or difficulty getting out of a chair, or difficulty getting up from a squatting position (eg. after toileting) without using the arms suggests proximal lower limb (hip girdle) weakness, while difficulty using the arms when performing above the shoulder level activities (eg. combing one's hair, lifting heavy objects off high shelves) suggests proximal upper limb (shoulder girdle) weakness; truncal weakness is suggested by an inability to sit up in bed without using the arms; distal weakness of the upper limbs is suggested by difficulties with wrist and hand movements and fine motor control (eg. tying shoelaces, doing up buttons, using writing and eating utensils, unscrewing screw-on jar lids)
 

Pattern of muscle weakness - likely source of weakness
Symptoms Likely source of weakness
 Slurred-nasal speech
 Drooling
 Nasal regurgitation of liquids
 Difficulty whistling, smiling
 Difficulty swallowing		  Bulbar muscles
 Diplopia
 Ptosis		  Extraocular muscles
 Trouble reaching for high shelves
 Difficulty shaving, combing hair, using hair dryer		  Proximal upper limb muscles
 Difficulty opening jars, doors, using keys or silverware  Distal upper limb muscles
 Difficulty rising from chairs and sofas
 Difficulty getting out of a car, bath or off a toilet
 Difficulty climbing stairs		  Proximal lower limb weakness
 Tripping when walking  Distal lower limb weakness

- after first establishing the presence of muscle weakness, it is useful to determine whether the weakness is bilateral and symmetric, or whether the weakness is asymmetric or focal

Bilateral weakness of all 4 limbs (both arms and both legs)

- bilateral weakness involving all 4 limbs is usually due to a myopathy, a neuromuscular junction disorder, a neuropathy, and rarely due to an upper-mid cervical myelopathy or brainstem or cerebral pathology

- the distribution of weakness can suggest a particular pathophysiology

- proximal muscle weakness suggests a myopathy rather than a neuropathy, which usually causes distal muscular weakness => distal muscle weakness can involve the hands (eg. difficulty with fine muscle movements of the hands when handling eating utensils, or when attempting to unscrew screw-on jar lids) and/or the feet (tripping over the curb or scuffing the feet when walking secondary to foot drop)

Distal weakness of both the upper and lower limbs is near-pathognomonic of a peripheral neuropathy

- another clue that suggests a myopathy is that the muscle weakness is usually global and it involves both the upper and lower limbs +/- trunk musculature, with major weakness of large muscle groups rather than small muscle groups

- a myopathy tends not to affect the bulbar muscles, and involvement of the motor cranial nerves (external ocular muscle weakness => diplopia, levator palpebrae superioris weakness => ptosis, face paralysis => face drooping and inability to grimace , pharyngeal muscle paralysis => dysphagia, tongue paralysis => dysarthria) in association with bilateral generalized muscle weakness suggests a neuromuscular junction disorder eg. myasthenia gravis or botulism

- an acute myopathy does not usually produce muscle atrophy, which is late sign of severe or progressive muscle disease and the degree of atrophy often parallels the extent of the progressive myopathy; acute muscle atrophy developing within days/weeks of the onset of weakness usually suggests a LMN (anterior horn cell or nerve root or peripheral nerve) lesion

- an acute myopathy may be associated with muscle tenderness +/- muscle swelling; muscle tenderness suggests an inflammatory or infectious myopathy (eg. polymyositis); muscle tenderness + swelling suggests trichinosis, clostridial myositis or other bacterial myositis; however, many myopathies produce profound muscle weakness without any muscle tenderness

(* a history of recurrent episodes of episodic muscle weakness accompanied by myoglobinuria suggests a genetic metabolic myopathy, and further metabolic investigations are warranted)

- tendon reflexes are retained in myopathic disorders until very late in the disease course, and early loss of deep tendon reflexes suggests a neuropathy

Normal reflexes in the upper limbs and absent reflexes in the lower limbs suggests a thoracic or lumbar spinal cord lesion

- a myopathy does not cause sensory loss, and any sensory deficit associated with motor weakness implies either a mixed sensorimotor peripheral neuropathy, a myelopathy or a brainstem/cerebral lesion
 

Key clinical features used to localize a neuromuscular disorder
 Myopathy
  • predilection for neck, limb girdle and proximal muscles
  • occasional respiratory muscle involvement
  • possible risk of myoglobulinuria
  • no sensory loss
  • normal tendon reflexes (early stage)
 Neuromuscular junction
  • cranial, limb girdle and proximal muscles
  • may affect respiratory muscles
  • no sensory loss
  • autonomic symptoms present if pre-synaptic
  • fatigueability when post-synaptic, post-exercise increase in strength when pre-synaptic
 Neuropathy
  • weakness and sensory signs
  • may have associated autonomic signs
  • may involve cranial nerves
  • tendon reflexes decreased or absent
 Motor neuron
  • predominantly motor signs
  • occasional sensory symptoms
  • often asymmetric
  • tendon reflexes may be increased if amyotrophic lateral sclerosis

- muscle tone is reduced in myopathic diseases and LMN lesions (eg. peripheral neuropathy), and increased muscle tone suggests an UMN lesion (spasticity)

(* spasticity is common in UMN lesions and the increased muscle tone is found in the flexor muscle muscles of the upper limbs and extensor muscles of the lower limb; by contrast, muscle rigidity usually involves both the flexor + extensor muscle groups of all the limbs and it may have a lead-pipe rigidity pattern eg. neuroleptic malignant syndrome, or a varying cogwheel rigidity pattern if there is a superimposed tremor eg. Parkinson's disease)

- bilateral muscle weakness involving all 4 limbs (tetraparesis) that is due to nervous system disease - and not muscle disease - can either be an UMN weakness (cerebral motor cortex pathology, corticospinal tract pathology in the brainstem or cervical spinal cord pathology) or LMN weakness (anterior horn cell, nerve root, or peripheral nerve)

- UMN weakness, if well-established (subacute or chronic), is associated with:-

(* however, acute UMN lesions often produce flaccidity, hypotonia and absent Babinski reponses - mimicing a LMN lesion)

- LMN weakness is associated with:-

A general rule is that if the weakness only involves an entire limb (monoplegia), both lower limbs (paraplegia), an upper and lower limb on the same side of the body (hemiplegia) or all 4 limbs (tetraplegia) - the causative lesion is most likely an UMN lesion in the CNS

LMN lesions usually involve a segment of a limb in a segmental or peripheral nerve pattern
 

Differentiation between UMN and LMN pathology
Clinical sign UMN LMN
Region Monoplegia, paraplegia, hemiplegia, tetraplegia Segmental - part of a limb
Muscle tone Increased (not early on) Decreased
Atrophy Minimal or absent Present (not early on)
Fasiculations Absent May be present
Reflexes Hyperreflexia (not early on) Hyporeflexic
Extensor plantar response Present (not early on) Absent

- an UMN lesion causing a UMN-type tetraparesis produces associated clinical signs depending on the site of pathology => see table
 

Bilateral weakness of the upper and lower limbs
  Myopathy Neuropathy Neuromuscular junction
Distribution of weakness Proximal Distal (initially) General
Ocular and bulbar muscle weakness Rare Infrequent Common
Muscle pain and/or tenderness +/- - -
Muscle atrophy Late Early -
Reflexes Preserved - early
Absent- late		 Absent - early Present
Sensory deficit Absent May be present Absent

 
Anatomic localization of a tetraparesis - due to UMN pathology
Location of lesion Pattern of neurological signs
Bilateral cerebral hemipsheres Tetraparesis, spastic dysarthria, dysphagia with hyperactive jaw jerks (pseudobulbar palsy), decorticate posturing (large acute lesions)
Midbrain Tetraparesis, coma, mid-sized poorly reactive pupils, decerebrate posturing
Basis pontis Tetraparesis, "locked in "syndrome, paralysis of horizontal gaze, paralysis of jaw and face and pharnyx and tongue muscles, preservation of consciousness and blinking and vertical eye movements
Cervicomedulllary junction Tetraparesis +/- involvement of pharnyx and tongue 
High cervical Tetraparesis, no cranial nerve palsies, no hyperreflexic jaw jerk
Mid cervical Tetraparesis + preserved shoulder movements

Bilateral weakness of the legs

- usually due to UMN pathology (cerebral motor cortex - bilateral, corticospinal pathways in the lower spinal cord) or LMN pathology (cauda equina pathology, lumbosacral plexus, peripheral nerves)

- localisation of UMN lesions is critically dependent on determining whether there is a sensory level, which suggests a spinal cord lesion rather than a cerebral lesion
 

Anatomic localization of a paraparesis due to UMN pathology
Location of lesion Pattern of neurological signs
Bilateral medial cerebral hemispheres (parasagittal lesion eg. meningioma)  Spastic paraparesis with no sensory level
Thoracic spinal cord Spastic paraparesis with thoracic sensory level and spastic bladder (* subacute or chronic)
Lumbar spinal cord Spastic paraparesis with lumbar level and spastic bladder (* subacute or chronic)

(* subacute or chronic spinal cord lesions produce spasticity, hyperreflexia and a spastic bladder, while acute spinal cord lesions may produce hypotonia and hyporeflexia and a flaccid bladder)

- a cauda equina lesion is usually associated with asymmetric LMN signs involving the lower lumbar and sacral nerve roots (weakness, hypotonia, hyporeflexia, and absent extensor plantar reflexes) leading to decreased strength of the glutei muscles, hamstrings, gastrocnemius and soleus muscles + saddle anesthesia +/- a flaccid bladder

- a polyneuropathy may start in the lower limbs and eventually ascend to involve the trunk and upper limb muscles eg. Guillain-Barre syndrome => it may therefore only produce bilateral lower limb weakness during the early stage of the disease

A polyneuropathy involving the lower limbs may produce a paraplegia, mimicing ACUTE transverse myelitis (or another acute transverse myelopathy), which is suggested by the presence of a sensory level + urinary retention in addition to the paraplegia

- certain myopathies preferentially cause lower limb weakness eg. chronic alcoholic myopathy

Asymmetric or focal muscle weakness

- asymmetric muscle weakness can be due to an unilateral UMN lesion causing a hemiparesis, or be due to an asymmetric LMN lesion eg. poliomyelitis

- focal weakness can be isolated (single anatomic site) or multifocal (multiple non-contiguous anatomic sites)

- multifocal weakness suggests multiple sclerosis or mononeuritis multiplex (usually due to DM, or vasculitis [eg. SLE, polyarteritis nodosa, rheumatoid arthritis], or sarcoidosis, or tuberculosis or Waldenstrom's macroglobulinemia)

- isolated focal weakness can be due to disease of the cerebrum, brainstem, spinal cord, nerve root, nerve plexus, or peripheral nerve

- localization of UMN diseases causing a hemiparesis depends on the associated clinical signs
 

Anatomic localization of a hemiparesis - due to UMN pathology
Location of lesion Pattern of neurological signs
Cerebral cortex Contralateral arm affected more than leg or face
+/- aphasia, apraxia, contralateral homonymous hemianopia (left hemisphere)
+/- contralateral homonymous hemianopia, inattention to left half of body, constructional apraxia (right hemisphere)
Internal capsule Contralateral arm equal to leg, face may be spared
No sensory loss or aphasia
Brain stem Contralateral arm equal to leg plus ipsilateral cranial nerve palsy
Midbrain Third nerve palsy (Weber syndrome)
Pons Sixth and seventh nerve palsy + ipsilateral gaze palsy (Foville syndrome)
Medulla Twelth nerve palsy
Cervical hemi-cord  Ipsilateral weakness of arm and leg; ipsilteral loss of proprioception and vibration sensation; contralateral loss of pain and temperature sensation (Brown-Sequard syndrome)

Episodic weakness

- there are many causes of intermittent or fleeting muscle weakness

- a TIA is a common cause of episodic UMN weakness

- other less common diseases mimicing a TIA include partial epileptic seizures, Todd's paralysis following a generalized convulsive seizure, and hemiplegic migraine

- rare causes of episodic muscle weakness include periodic paralysis syndromes

- certain diseases causing episodic muscle weakness may result in drop attacks (eg. catalepsy, sleep paralysis associated with hypnogogic hallucinations, Arnold-Chiari malformations or unstable alanto-axial joints compressing the cervicomedullary junction) => see the "drop attacks" section of the gait disorders, drop attacks and frequent falls guidemap for further details
 
Clinical decision-making in an ED setting

- an emergency physician should always be alert to any alterations in the vital signs (tachycardia, hypotension, hyperpyrexia) that may suggest a systemic disease causing "weakness", and some examples include:-

- if the vital signs are normal, and the clinical presentation suggests a neuromuscular disorder causing generalized muscle weakness (rather than non-specific weakness), then an emergency physician needs to perform a thorough neurological examination in order to accuratedly differentiate the various sub-categories of neuromuscular weakness (myopathy, NM junction disorder, neuropathy, UMN or LMN pathology)

- essential neurological examination elements include an evaluation of:-

- is should be possible, after performing a targeted neurological examination, to have a good idea whether the patient has a myopathy, neuropathy, UMN lesion or a neuromuscular transmission disorder as the likely cause of the acute neuromuscular weakness

- combining that pathophysiological knowledge with common-sense knowledge regarding the frequency of certain diseases, it should be possible to make a sensible tentative diagnosis

- for example, a young patient with an ascending paralysis (over a few days), who has presenting sensory dysesthesias and paresthesias, but no sensory loss + absent/reduced deep tendon reflexes, is likely to have acute demyelinating inflammatory polyradiculopathy (Guillain-Barre syndrome)

- when faced with that presentation, an emergency physician should always ensure that there is no sensory level, which suggests a transverse myelopathy; that there there are no ticks hidden in the scalp hair, which suggests tick paralysis; and that fever and meningeal signs are absent, which suggests acute poliomyelitis
 

Clinical features of some diseases causing an ascending paralysis
Clinical feature Tick paralysis ADIP Spinal cord lesion Poliomyelitis
Rate of progession Hours to days Days to weeks Abrupt or gradual Days to weeks
Tendon reflexes Absent Absent Variable - normal reflexes above the lesion and absent reflexes (acute) or hyperactive reflexes (subacute) below the lesion Absent
Extensor plantar response Absent Absent Absent (acute)
Present (subacute)		 Absent
Sensory signs None Rare (distal limbs) Present (sensory level - below the lesion) Absent
Meningeal signs or fever Absent Rare Absent-rare Present

- if the patient presents with oculo-bulbar paralysis +/- descending paralysis, then one should first think of myasthenia gravis and botulism; the presence of pupillary paralysis + other autonomic signs suggests botulism; and a history of episodic weakness and a fatigueability phenomenon suggests myasthenia gravis; associated ataxia should make one think of the Miller-Fisher variant of ADIP

- if the patient presents with an acute myopathic presentation (proximal muscle weakness + no sensory findings + normal reflexes + no bladder/bowel dysfunction), then one should first determine whether the myopathy is painless or painful

- acute painless myopathy is most likely due to one of the periodic paralysis syndromes, an electrolyte disorder (eg. hypokalemia or hypercalcemia) or a toxic myopathy (drugs or toxins)

- acute painful myopathy is most likely due to a toxic myopathy (alcohol, certain drugs or toxins) or an inflammatory myopathy (eg. polymyositis) or infectious myositis (eg. trichinosis, toxoplasmosis, viral or bacterial myositis)

(* the presence of muscle tenderness + swelling +/- crepitus+/- myoglobinuria strongly suggests an infectious or necrotizing myositis)

- occasionally, a patient may present to the ED with rapidly progressive muscle weakness that is so profound, that it may be difficult for the clinician to clearly differentiate a neuropathy from a myopathy (or other cause of profound muscle weakness), because of the patient's inability to speak or fully cooperate during a neurological examination

If the patient appears to have profound muscle weakness of acute onset and cannot readily speak, an emergency physician should have a low threshold for prophylactic intubation and mechanical ventilation

- clinical clues that suggest respiratory failure secondary to muscle weakness, or a need for intubation include:-

- there are no "fixed" clinical criteria mandating prophylactic intubation, and clinicians should use judicious clinical judgment and meticulous, continued observation of the patient during the initial clinical evaluation stage to avoid being caught off guard

(* an ABG showing hypercarbia is a definite indication for intubation and mechanical ventilation, but clinicians should not wait for laboratory evidence of alveolar hypoventilation before considering prophylactic intubation; if a patient can take a maximal inspiration and then count up to 25, the FVC is probably about 2 litres - while an ability to slowly count to 10 suggests a probable FVC of 1 litre)

- if the patient has profound bilateral muscle weakness of rapidly progressive onset, the following neuromuscular conditions should be considered in the differential diagnoses

Muscle disorders

Neuromuscular junction disorders Peripheral nerve disorders Motor neuron disorders Spinal cord disorders UMN tetraparesis - if the diagnosis is not readily apparent, then the history should focus on obtaining more information from any clinical clues that may suggest a particular diagnosis

Is there a pre-existing neuromuscular disorder or has the condition arisen de novo?

- several inherited neuromuscular disorders may undergo rapid progression in their final stages and produce respiratory failure (X-linked dystrophies, acid maltase deficiency), while diseases such as myasthenia gravis may produce recurrent episodes of profound weakness in the presence of infection, stress or precipitating drugs

- prior episodes of painless weakness suggest familial periodic paralysis; recurrent attacks of exercise intolerance [proximal muscle weakness + muscle cramping and muscle tenderness + myoglobulinuria after performing physical exercise] suggest an inborn error of glycogen metabolism (after a short bout of heavy exercise) or lipid metabolism (after a bout of prolonged mild-to-moderate exercise or exercise in a relatively fasted state)

Is there a history of an underlying malignancy?

- an underlying malignancy suggests the possibility of LEMS, or paraneoplastic neuropathy, or chemotherapeutic drug-induced myopathy (eg. cyclosporin)

Is there any underlying systemic disease?

- a myopathy may be due to hypothyroidism, hyperthyroidism, Cushing's disease, dermatomyositis, polymyositis

- a polyneuropathy may be due to rheumatoid arthritis, systemic lupus erythematosis, polyarteritis nodosa or cryoglobulinemia

What prescription or non-prescription drugs is the patient taking?

- certain drugs may induce myotoxicity eg. cholesterol-lowering agents, colchicine, choloroquine, cyclosporine and L-tryptophan (see table for a more complete list)

- recent use of oral contraceptives or anti-convulsants suggest the possibility of acute intermittent porphyria

- excessive use of diuretics may induce hypokalemia and secondary hypokalemia-induced muscle weakness

- magnesium-antacid overuse in the presence of renal failure may produce hypermagnesemic weakness, or precipitate an attack of myasthenia gravis in vulnerable patients

- high-dose steroids can induce an acute steroid-induced myopathy - especially if the patient is immobile, has concurrent sepsis or is receiving neuromuscular blocking drugs

What is the dietary and exercise profile of the last 48 hours?

- recent marine shellfish consumption suggests shellfish poisoning

- recent consumption of home-canned food suggest botulism

- recent consumption of undercooked pork or game (wild boar, bear, horse) suggests trichinosis

- a large carbohydrate meal following a period of rest after heavy exercise may induce periodic paralysis

- sudden weakness following a large glucose load in a malnourished patient suggests the possibility of acute hypophosphatemic paralysis

- a bout of heavy alcohol consumption may induce an acute alcoholic myositis, and severe cases may develop rhabdomyolysis (history of "coca-cola" coloured urine); alcoholics are also prone to develop acute hypokalemic alcoholic myopathy due to severe underlying hypokalemia, or hyphosphatemic paralysis following a sudden large glucose load

Was there potential exposure to tick bite, snake bite, or a neurotoxin?

- inquire about occupational exposures (volatile solvents such as carbon tetrachloride or toluene, or arsenic used in lead and copper smelting) or recreational exposures to potential neurotoxins (volatile hexacarbon solvents causing sensorimotor neuropathy eg. glue sniffing - teenagers "huffing" from a paper bag)

- a recent woodland exposure suggests the possibility of tick paralysis

- farm exposure to pesticides containing organosphosphates suggests the possibility of a polyneuropathy (predominantly motor polyneuropathy 1 - 3 weeks after acute exposure mainly affecting the legs => upper limbs after a few days)

In addition to weakness, are there sensory or autonomic symptoms?

- bizarre sensory symptoms suggest shellfish poisoning

- sensory paresthesias suggest a neuropathy or myelopathy

- a painful band of paresthesia around the trunk suggests the locality of an acute myelopathy eg. transverse myelitis

- prominent autonomic symptoms are seen in botulism, organophosphate poisoning and some polyneuropathies

First think of common neuromuscular disorders --- acute demyelinating inflammatory polyradiculopathy (Guillan-Barre syndrome) is the most common cause of acute generalized muscle weakness; other acute NM diseases that should initially be considered include myasthenia gravis, botulism, tick paralysis, periodic paralysis, toxic myopathies, and spinal cord disorders

- if the diagnosis is not readily apparent, the following clinical clue table offers an emergency physician a memory-jogging checklist of some causes of rapildy progressive neuromuscular weakness and their associated clinical findings

(* some of these diseases produce chronic neuromuscular weakness, and they may only produce rapidly progressive weakness under certain circumstances, or as an end-stage phenomenon; some of the listed myopathies are rare congenital disorders that occur very infrequently)
 

Muscle disorders
 Myoglobinuric myopathy
  • severe limb girdle and proximal muscle weakness
  • muscle swelling, aches and pains
  • markedly elevated serum CK and myoglobulinuria
  • see the myopathy and myoglobulinuria guidemap for further details
 Periodic paralysis
  • many different variants
  • often presents with disproportionate proximal muscle weakness of the trunk and lower limbs
  • patients with hypokalemic periodic paralysis tend not to develop respiratory failure
  • history of awakening with early am weakness, often preceded by history of heavy exercise followed by rest and/or a heavy meal the day before presentation
  • weakness lasts hours to days
  • a specific hypokalemic variant seen in young adult oriental patients with occult thyrotoxicosis
  • see the myopathy and myoglobinuria guidemap for further details
 Toxic myopathy
  • proximal and limb girdle weakness
  • muscle cramps and muscle tenderness
  • often markedly elevated serum CK
  • alcoholic patients may develop acute alcoholic mysositis secondary to binge drinking, or hypokalemic-induced or hypophosphatemic-induced paralysis
  • chronic abusers of volatile solvents (eg. toluene or hobby glues) may develop severe symmetric muscle weakness in association with peripheral neuropathy, spasticity, ataxia and dementia; the weakness is associated with hypokalemia and elevated serum CK +/- rhabdomyolysis
  • drugs-of-abuse (cocaine, phencyclidine, heroin and amphetamines) may also produce a toxic myopathy and rhabdomyolysis
  • diuretics, licorice, carbenoxolone, amphotericin B can produce an acute hypokalemic-induced myopathy
  • certain prescription drugs can produce a painful toxic myositis (penicillamine, procainamide, phenytoin, levodopa, cimetidine, leuprolide, propylthiouracil)
  • cholesterol-lowering agents (gemfibrizol, clofibrate, lovastatin, simvastatin) may also produce an acute toxic myopathy, especially if multiple agents are taken together, or if taken with immunosuppressive agents (eg. cyclosporin), or in the presence of renal failure
  • carbon monoxide, arsenic, cyanide and snake venom can induce muscle necrosis and secondary myoglobinuria
  • see the myopathy and myoglobulinuria guidemap for further details
 Polymyositis and dermatomysositis
  • severe proximal limb (legs > arms) and neck muscle weakness of gradual onset
  • history of muscle pains, morning stiffness, fatigue, weight loss +/- fever common (mimics polymyalgia rheumatica but the myalgias are usually less severe)
  • ocular muscles not involved, oropharyngeal muscles rarely involved
  • may sometimes have muscle tenderness and swelling
  • symmetrical peri-orbital heliotrope rash (violaceous to dusky rash +/- edema), erythematous rash over face and upper trunk, and Gottron's papules over the knuckles is characteristic of dermatomyositis
  • dysphagia (without tongue dysarthria or extraocular involvement) and polyarthritis occur in both conditions
  • may overlap with other connective diseases (eg. mixed connective tissue disease, rheumatoid arthritis, scleroderma, Sjogrens syndrome and systemic lupus erythematosis) and many other auto-immune diseases
  • increased risk of an associated malignancy (especially in dermatomyositis patients > 50 years)
  • myositis-specific antibodies may be present
  • serum CK increased to 5 - 50x normal
 Trichinosis myositis
  • GIT symptoms begin 2 - 3 days after parasite ingestion (undercooked pork or game)
  • fever, malaise, vomiting, diarrhea, peri-orbital edema of the face 
  • severe myalgia common
  • stiff, swollen tender muscles
  • extraocular muscles, masseters, larynyx, tongue, neck muscles, diaphragm, intercostals, limb flexors and lumbar muscles are most frequently involved; quadriplegia rare
  • cardiomyopathy and CNS involvement rare
  • leucocytosis (65%), eosinophilia common after 10 days, positive serology delayed 2 - 3 weeks, elevated serum CK ++
 X-linked dystrophy
  • most common types include Duchenne's muscular dystrophy and Becker's muscular dystrophy => Duchenne's muscular dystrophy presents in early childhood with running difficulties and difficulty climbing stairs => lower extremity, lower trunk and pelvic girdle weakness
  • progressive severe generalized weakness, sparing cranial muscles, with joint contractures of the lower limbs common
  • may result in ventilatory failure with death before the end of the second decade
  • associated hypertrophic cardiomyopathy
 Myotonic dystrophy
  • most common muscular dystrophy in adults
  • generalized weakness, involving cranial nerves and distal muscles, with myotonia common 
  • weakness of facial muscles, with characteristic temporalis and masseter muscle atrophy; face is hatched and thin with ptosis and frontal balding; disproportionate sternocleidomastoid muscle weakness compared to other shoulder and neck muscles
  • may produce ventilatory failure
  • tendon reflexes may be reduced or absent
  • associated findings include cardiomyopathy, which can cause sudden death 
 Acid maltase deficiency (glycogenolysis type II)
  • three forms - infantile, childhood and adult forms
  • due to a deficiency in lysosomal alpha-glucosidase
  • infantile form (Pompe disease) presents in the first few months of life with hypotonia, weak bulky muscles, macroglossia, hepatomegaly, cardiomegaly, congestive heart failure => progressive disease => death in 1 - 2 years from respiratory failure or other complications
  • childhood form produces proximal muscle weakness, +/- muscle hypertrophy; respiratory muscle involvement common => may produce ventilatory failure
  • adult form presents after age 20 years with progressive proximal muscle weakness (especially diaphragm, biceps, shoulder, and thigh adductors); respiratory failure is the presentation in 30% of patients and it eventually occurs in 100% of patients
 Mitochondrial myopathy
  • generalized weakness and ophthalmoparesis
  • exercise intolerance; muscle cramps and myoglobinuria rare
  • excessive lacticacidosis at rest with excessive rise after mild exercise
  • may produce ventilatory failure
Neuromuscular junction disorders
 Myasthenia gravis
  • pathologic hallmark is muscle fatigueability
  • weakness may be precipitated by infection, drugs, heat, stress, menses or pregnancy
  • chronic and fluctuating course
  • predominance of ocular and bulbar involvement (ptosis, diplopia, dysphagia, dysarthria)
  • upper limbs usually affected more than lower limbs
  • respiratory muscle involvement may produce ventilatory failure
  • episodic weakness is worse as the day proceeds and is aggravated by exercise, and relieved by rest
  • myasthenic crisis may be precipitated by drugs (see list in the appendix)
  • normal pupillary responses, normal deep tendon reflexes and no sensory loss
  • positive response to tensilon
  • aggravation of weakness following tensilon administration suggests a cholinergic crisis 
 Lambert-Eaton myasthenic syndrome (LEMS)
  • gradual onset of fluctuating proximal weakness mainly involving the legs producing a waddling gait
  • muscle fatigibility common, mild exercise may increase muscle strength (this "warming-up" phenomenon is the opposite to the fatigueability phenomenon seen in myasthenia gravis)
  • sustained exercise, heat or fever may aggravate weakness
  • muscles may ache and are occasionally tender
  • tendon reflexes may be reduced or absent, but reflexes improve with repeated testing
  • ocular and oropharyngeal muscles rarely affected (opposite of myasthenia gravis)
  • respiratory failure uncommon
  • may be discovered because of prolonged recovery following use of neuromuscular blocking agents during anesthesia for surgery
  • may be exacerbated by drugs - aminoglycoside or fluoroquinone antibiotics, magnesium, calcium channel blockers, iodinated IV contrast media 
  • no sensory loss
  • associated with underlying malignancy (small cell carcinoma of lung most common), and muscle weakness may precede the malignancy
  • dry mouth (hypo-salivation) and perversion of taste (metallic mouth taste) is a common associated complaint; other dysautonomias may occur (hypohidrosis and impotence)
  • weakness may rarely respond positively to tensilon (false-positive test)
 Botulism
  • rapidly progressive muscle weakness, often starting in the extraocular and pharyngeal muscles (diplopia, blurred vision, ptosis, dysarthria and dysphagia) => upper limb weakness => lower limb weakness => respiratory failure (descending paralysis)
  • no sensory signs
  • accomodative paresis and 6th nerve palsies are early signs
  • fixed dilated pupils common (50%)
  • other autonomic symptoms common (bradycardia, hypotension, hypohydrosis, constipation, ileus and dry mouth)
  • history of consuming home-canned foods 12 - 24 hours prior to symptoms
  • wound botulism (eg. drug abusers using black tar heroin => skin popping => sc abscesses or muscle abscesses) may produce delayed symptoms (1 - 2 weeks after wound contamination)
  • no response to tensilon => empiric treatment may be necessary if the tensilon test is negative and ADIP and tick paralysis are excluded, and the etiology remains uncertain 
 Hypermagnesemia
  • seen in eclamptic patients treated with parenteral magnesium, or in patients with renal failure and magnesium-antacid abuse
  • serum magnesium usually > 10 mg/dl
  • ocular, cranial and respiratory weakness can occur
  • associated with metabolic encephalopathy
Peripheral nerve disorders
 Acute inflammatory demyelinating polyradiculopathy (Guillan-Barre syndrome)
  • the most common cause of acute generalized neuromuscular weakness
  • usually produces an ascending symmetric paralysis starting distally in the legs and then ascending over a few days + absent DTRs + sensory paresthesias +/- no sensory loss
  • mild-to-moderate distal limb paresthesias may precede weakness by 1 - 2 days
  • the presence of normal reflexes in the presence of severe generalized weakness virtually rules-out the diagnosis; a sharp sensory level or asymmetric weakness or marked bowel or bladder dysfuction at the onset rules-out the diagnosis
  • usually progesses over days/weeks, but may be rapidly progressive over 24 - 48 hours
  • many different variants, and may present with proximal > distal weakness, upper limb > lower limb weakness
  • some patients may have sensory deficits - especially loss of vibration and proprioceptive sensation
  • 50% of cases are associated with cranial nerve involvement, oropharyngeal weakness, and autonomic dysfunction (labile hypertension, tachycardia and decreased sweating) - the degree of dysautonomia may parallel the degree of weakness 
  • may produce respiratory weakness, which can correlate with the degree of impairment of shoulder elevation and neck flexion
  • Miller-Fisher variant consists of total external ophthalmoplegia, loss of tendon reflexes and ataxia; patient often presents with diplopia, clumsiness and gait disorder; oropharyngeal weakness less common; no vertigo, nystagmus or cerebellar dysarthria; weakness may  progress to a descending paralysis (mimicing botulism) 
  • often preceded by a viral syndrome or gastro-enteritis picture a few weeks before acute paralysis
  • other associations include viral hepatitis, mycoplasma, Lyme disease, sarcoidosis, Hodgkins lymphoma, organ transplantations and recent vaccinations
  • normal CSF in the first 24 - 48 hours; abnormal CSF findings seen after a few days => increased CSF protein and no cells (albuminocytologic dissociation); 5 - 10% of patients have a CSF lymphocytosis of < 100 cells/cu.mm
  • immunologic disorder associated with patchy demyelination of nerve roots and peripheral nerves
  • axonal degeneration seen in cases associated with Campylobactor infection and anti-GM1 ganglioside IgG antibodies => severe paralysis is common
 Tick paralysis
  • north-western USA
  • irritability and myalgia < 7 days after tick attachment
  • rapidly ascending flaccid paralysis over 1 - 3 days
  • cranial nerve involvement common, respiratory failure rare
  • ataxia and sensory changes rare, DTRs decreased or absent
  • rapid improvement following tick removal (often imbedded in the scalp)
 Vasculitic neuropathy
  • multiple overlapping neuropathies
  • asymmetric onset, with rapid evolution to generalized weakness, sensory loss and pain
  • usually occurs in the context of systemic vasculitis signs
  • seen in systemic lupus erythematosis, scleroderma, polyarteritis nodosa, rheumatoid arthritis, cryoglobulinemia and many other vasculitidies
  • see this website for further problem-solving information http://www.neuro.wustl.edu/neuromuscular/antibody/pnimax.html#vasculitis 
 Acute intermittent porphyria
  • attacks may be precipitated by drugs (barbiturates, phenytoin, sulfonamides, estrogens)
  • attacks can also be precipitated by prolonged fasting, infection or menses
  • symmetric polyneuropathy with prominent motor weakness and lesser sensory loss (arms > legs); severe paresthesias may occur
  • associated with abdominal pain, altered mental status (confusion or delirium or pschosis)
  • may be accompanied by autonomic instability (fever, tachycardia, hypertension), hyponatremia and leucocytosis
 Acute diptheritic neuropathy
  • first presents with palatal weakness a few weeks after an infected sore throat
  • a local cranial polyneuropathy with paralysis of pupillary accomodation, nasal speech due to palatal paralysis, dysphagia and respiratory compromise may occur 3 - 4 weeks after the initial throat infection; pupillary light reaction is normal
  • a secondary generalized sensorimotor neuropathy may follow (8 - 12 weeks after infection) - which can be asymmetric, and occasionally proximal greater than distal; severe myalgia may occur
  • respiratory paralysis occurs in severe cases
 Arsenic neuropathy
  • the most common form of acute heavy metal poisoning in the USA
  • subacute sensorimotor polyneuropathy mimicing Guillain-Barre syndrome
  • painful distal paresthesias common
  • associated encephalopathy and systemic symptoms common
  • subacute toxicity may produce skin pigmentation, eczematous rashes, Mees' lines and Raynaud's acrocyanosis
  • causes include accidental exposure to weed killers or insecticides, history of drinking well water or contaminated wine or moonshine, occupational exposure (metal ore smelting) or intentional homicidal poisoning
 Shellfish toxins
  • tetrodotoxin (pufferfish)
  • ciguatoxin (ciguatera)
  • saxitoxin (paralytic shellfish poisoning)
  • brevitoxin (neurolytic shellfish poisoning)
  • often associated with gastro-enteritis symptoms
  • rapildy progressive peripheral neuropathy develops within minutes-hours of marine fish ingestion => ascending paralysis
  • bizarre and/or painful sensory symptoms common
 Hypophosphatemia
  • seen in parenteral hyperalimentation, acute alcohol intoxication, starvation followed by a large glucose load, phosphate-binding antacids, and rarely in DKA
  • serum phosphate usually < 1.0 mg/dl, often < 0.5mg/dl
  • pronounced paresthesias of the hands, feet and peri-oral area are the earliest symptoms => generalized weakness follows
  • hypoactive or absent tendon reflexes
  • ocular, cranial and respiratory weakness can occur
  • associated encephalopathy common
Motor neuron disorders
 Amyotrophic lateral sclerosis
  • usually produces generalized weakness with marked atrophy and fasiculations
  • weakness may be patchy and asymmetric
  • oropharyngeal weakness common (bulbar onset in 20 - 30% of cases)
  • typical pattern is combined UMN and LMN signs
  • tendon reflexes may be pathologically brisk, especially in the lower limbs
  • respiratory failure may occur in isolation; early suggestive symptoms may include sleep disorders, dyspnea or morning headache; associated with weight loss, loss of sense of taste and depression
  • see this website for further problem-solving information http://www.neuro.wustl.edu/neuromuscular/spinal/als.htm 
 Poliomyelitis
  • presents with acute febrile viral meningitis syndrome followed by asymmetric limb weakness within 2 - 5 days
  • patient may suffer from intense myalgias and hyperalgesia
  • weakness may be fulminant, acute or subacute; pattern may be legs > arms > bulbar
  • autonomic dysfunction may be prominent (blood pressure lability, arrhythmias, constipation and ileus, hyperhydrosis or hypohydrosis, urinary retention)
  • electrophysiologic studies can differentiate polio from a peripheral neuropathy
  • can follow oral polio vaccine administration in patients with an immunologic disorder eg. hypogammaglobulinemia
Spinal cord disorders
 Transverse myelitis
  • sudden onset of paraplegia + sensory level (all sensory modalities lost below that level) + band of paresthesia at level of lesion + inability to void (developing over hours-days)
  • prodrome:- febrile illness 37% vaccination 15% 
  • isolated cases may follow a recent viral infection (EBV, CMV, rubella, hepatitis, measles, HIV, HTLV-1); may also be due to multiple sclerosis, mycoplasma, herpes zoster, tuberculosis, syphilis, sarcoidosis, systemic lupus erythematosis and antiphospoholipid antibody syndrome
  • differentiated from AIDP and other neuromuscular causes of sudden weakness by a "sensory level" +/- bladder involvement (40%) and erectile dysfunction (90%)
 Spinal cord infarction
  • usually due to anterior spinal artery obstruction eg. aortic dissection, trauma, vasculitis, hypotensive episode in narrowed artery, scuba diving and secondary air embolism
  • involves the thoracic or caudal spinal cord => sudden flaccid, areflexic paraparesis + dissociated sensory loss (loss of pain and temperature sensation + retention of vibration and proprioceptive sensation) + inability to void
 Spinal cord compression syndrome
  • sudden back pain + paraplegia + sensory level
  • acute etiologies include tumor (primary or metastatic), epidural abscess, epidural hematoma, vascular malformation and herniated disc
  • see the low back pain guidemap for further details

Diagnostic workup of acute neuromuscular weakness

- the diagnostic workup may be limited if the clinical diagnosis is certain eg. ADIP, periodic paralysis, or UMN tetraparesis

- it is always worthwhile to obtain baseline bloodwork - CBC, serum electrolytes, serum calcium, magnesium and phosphate (+/- serum CK if a myopathy is a diagnostic consideration)

- a more extensive diagnostic workup may be required if the diagnosis is uncertain, and the following diagnostic tests should be considered, and selectively performed

- if the clinical picture suggests a myopathy, and the diagnosis is not clear; or if the myopathic clinical presentation is associated with myoglobinuria => the following sub-guidemap on myopathy and myoglobinuria may provide more information that may be useful in determining the likely cause of the myopathy

- patients with rapidly progressive muscle weakness are at risk of respiratory failure, and admission to an ICU for observation and regular VC monitoring may be warranted

Consult this excellent website for detailed information on neuromuscular disorders

http://www.neuro.wustl.edu/neuromuscular
 
Appendix

Medical Research Council rating of muscle strength

Grade 1 = no contraction
Grade 2- = flicker or trace of contraction
Grade 2+ = active movement, with gravity eliminated
Grade 3 = active movement against gravity
Grade 4- = active movement against light resistance
Grade 4 = active movement aginst moderate resistance
Grade 4+ = active movement against heavy resistance
Grade 5 = normal muscle power

Practical muscle strength testing

- a quick sensitive test for upper limb muscle weakness is to check for pronator drift => the patient is instructed to lift both upper limbs to shoulder level with both forearms held in front in supination with palms-up => a slow pronation and downward drift of the arms suggests muscle weakness

- a quick sensitive test for lower limb muscle weakness is to get the supine patient to elevate the thigh against gravity and active resistance, and to ambulate on the toes and heels

- neck extensor and neck flexor strength is tested against gravity and active resistance

- muscle strength above the neck is tested by asking the patient to pout, elevate the eyebrows, close the eyelids forcefully, blow the cheeks-out (7th cranial nerve); keep the jaw closed against active attempts to open the mouth, move the jaw from side-to-side (5th cranial nerve); push the tongue against a tongue blade held to the left and right of the mouth (12th cranial nerve)

- more thorough limb muscle strength testing can be achieved by testing a multiplicity of limb joint movement strengths, and it is most useful when localising the level of a spinal cord lesion or differentiating proximal from distal muscle weakness eg. upper limb - arm abduction at the shoulder (C5), elbow flexion (C5,6) and extension (C6,7), wrist flexion (C6,7,8) and extension (C6,7), finger flexion (C8, T1) and extension (C7); lower limb - hip flexion (L1, 2,3) and extension (L5, S1), knee flexion (L4,5,S1,2) and extension (L3,4), foot plantar flexion (S1) and dorsiflexion (L5)

Motor testing

- there is no "pure" single nerve testing of the upper and lower limbs

- some easy-to-remember combinations include:-

- the biceps reflex is C5/6, triceps reflex is C7/8, knee reflex is L3/4 and the ankle reflex is S1

(* although many textbooks/journal articles suggest that first toe dorsiflexion innervation is primarily from L5, other textbooks/journal articles suggest S1 as the major innervation=> because of this discrepancy in opinions, it is recommended that you use foot and small toe(s) dorsiflexion for L5 testing and plantar flexion of the foot for S1 testing)

- detailed muscle strength testing is useful in patients with asymmetric or focal weakness, and it may enable a physician to differentiate between a plexopathy, radiculopathy or peripheral nerve pathology
 

Detailed muscle strength testing - upper limb
Muscle Segmental nerve supply Peripheral nerve Muscle action
Deltoid C5 Circumflex Arm abduction
Infraspinatus C5 Suprascapular External rotation of the arm
Serratus anterior C5,6,7 Long thoracic nerve Patient pushes arm - held forward 90 degrees- against firm obstruction => muscle prevents scapular winging
Latissimus dorsi C7 Nerve to latissimus dorsi Adducts arm - held in abduction - towards chest
Biceps C5 Musculocutaneous Elbow flexion
Triceps C7 Radial Elbow extension
Extensor carpi radialis longus C6,7 Radial Extension of the wrist radially
Extensor carpi radialis ulnaris C7 Radial Extension of the wrist ulnarly
Extensor digitorum C7 Radial Finger extension at MP joints
Flexor carpi radialis C6,7 Median Wrist flexion radially
Flexor carpi ulnaris C8 Ulnar Wrist flexion ulnarly
Abductor pollicis longus C8 Radial Thumb abduction at MP joint
Extensor pollicis brevis C8 Radial Thumb extension at MP joint
Extensor pollicis longus C8 Radial Thumb extension at thumb IP joint
Opponens pollicis T1 Median Opposition of thumb to small finger
Abductor pollicis brevis T1 Median Abduction of thumb at MP joint
Flexor pollicis longus C8 Median Flexion of the thumb IP joint
Adductor pollicis T1 Ulnar Thumb adduction
Lumbricals and interossei C8,T1 Lumbricals I, II - Median
Interossei and lumbricals III and IV - Ulnar		 Flexion of the extended fingers at the MP joint (lumbricals)
Finger abduction (interossei)
Flexor digitorum sublimus C8 Median Finger flexion at PIP joint
Flexor digitorum profundus C8 Median - I, II
Ulnar - II, IV		 Finger flexion at DIP joint
Abductor digiti minimi T1 Ulnar Abduction of little finger

 
Detailed muscle strength testing - lower limb
Muscle Segmental nerve supply Peripheral nerve Muscle action
Iliopsoas L1,2,3 Femoral Thigh flexion
Adductor femoris L5, S1 Obturator Thigh adduction
Gluteus medius L4, 5, S1 Superior gluteal Thigh abduction
Gluteus maximus L5, S1 Inferior gluteal Thigh extension
Hamstrings of thigh L5, 5, S1, 2 Sciatic Knee flexion
Quadriceps femoris L3, 4 Femoral Knee extension
Tibialis anterior L4, 5 Deep peroneal Foot dorsiflexion
Tibialis posterior L4 Tibial Foot plantar flexion and inversion
Peronei L5, S1 Superficial peroneal Foot eversion
Gastrocnemius S1 Tibial Foot plantar flexion
Extensor digitorum longus L5 Deep peroneal Toe dorsiflexion
Flexor digitorum longus S1, 2 Tibial Toe plantar flexion
Extensor hallucis longus L5, S1 Deep peroneal Hallux dorsiflexion

 
Muscle stretch reflexes
Reflex Segmental innervation Nerve
Jaw jerk Pons Trigeminal - mandibular branch
Biceps jerk C5, C6 Musculocutaneous
Brachioradialis jerk C5, C6 Radial
Triceps jerk C7, C8 Radial
Finger jerk C8, T1 Median
Knee jerk L3, L4 Femoral
Ankle jerk S1, S2 Tibial

 
Drugs precipitating or aggravating neuromuscular weakness
 Drugs that cause motor neuropathy
  • dapsone
  • imipramine
  • certain sulfonamides
 Drugs associated with myopathy
  • beta-blockers
  • chloroquine
  • clofibrate
  • corticosteroids
  • drugs causing hypokalemia
  • emetine
  • epsilon-aminocaproic acid
  • penicillamine
  • zidovudine
  Drugs that can impair neuromuscular transmission
  • ACTH
  • aminoglycoside antibiotics
  • beta blockers
  • choloroquine
  • colistin
  • corticosteroids
  • lithium
  • magnesium-containing cathartics
  • penicillamine
  • phenothiazines
  • polymixin
  • procainamide
  • quinine
  • quinidine
  • tetracycline
  • vancomycin

Disclaimer: My EM guidemaps reflect my personal approach to problem-solving/managing clinical cases in an ED setting and they should not be regarded as the standard of care. They merely represent the personal opinions of the author and they should only be used in clinical practice if the reader-user has substantial reason to believe that the clinical advice contained in the guidemaps is valid and accurate. The guidemaps are not meant to be "authoritative" and the reader-user should consult standard medical textbooks and expert opinion articles/guidelines for more authoritative advice. The reader-user should particularly confirm all drug doses, their indications and contra-indications, prior to their use.