Diseases » Primary Hyperaldosteronism » Diagnosis

Diagnosis of Primary Hyperaldosteronism

Primary Hyperaldosteronism Diagnosis: Book Excerpts

• Ask the following questions - ALKALOSIS (INCREASED PH)
• Differential Diagnosis - Muscle Weakness – Proximal
• Differential Diagnosis - Muscle Weakness – Distal
• Approach to the Diagnosis - ALKALOSIS (INCREASED PH)
• History and physical examination - Weight gain, excessive
• History and physical examination - Muscle weakness
• History and physical examination - Weight loss, excessive
• History and physical examination - Gait, steppage [Equine gait, paretic gait, prancing gait, weak gait]
• Diagnosis - Hyperaldosteronism
• History and physical examination - Weight gain, excessive
• History and physical examination - Muscle weakness
• History and physical examination - Weight loss, excessive
• History and physical examination - Gait, steppage [Equine gait, paretic gait, prancing gait, weak gait]
• Diagnosis - Hyper-aldosteronism
• History - Weight gain, excessive
• History - Muscle weakness
• History - Weight loss, excessive
• Clinical Features and Diagnosis - Hypotonia and Weakness
• History and physical examination - Weight gain, excessive
• History and physical examination - Muscle weakness
• History and physical examination - Weight loss, excessive
• History and physical examination - Gait, steppage [Equine gait, paretic gait, prancing gait, weak gait]
• Approach to the Diagnosis - ALKALOSIS (INCREASED pH)

Diagnostic Tests for Primary Hyperaldosteronism: Online Medical Books

16 MEDICAL BOOKS ONLINE! Review excerpts from medical books online, free, without registration, for more information about diagnostis of Primary Hyperaldosteronism.

ALKALOSIS (INCREASED PH): Ask the following questions:
(Algorithmic Diagnosis of Symptoms and Signs)

1. What is the bicarbonate level? If this is elevated, the patient has a metabolic alkalosis. If this is decreased, the patient has a respiratory alkalosis associated with salicylate intoxication or hyperventilation syndrome.
2. Has the patient been vomiting? If so, look for gastric outlet obstruction, intestinal obstruction, and other causes of vomiting. If there is no history of vomiting, the alkalosis may be due to diuretics, Cushing's disease, or chronic antacid use.

DIAGNOSTIC WORKUP

The workup of alkalosis should include a CBC, chemistry panel, urinalysis, electrolytes, arterial blood gas analysis, flat plate of the abdomen, chest x-ray, and consultation with an endocrinologist.

 

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Source: Algorithmic Diagnosis of Symptoms and Signs, 2003

Muscle Weakness – Proximal: Differential Diagnosis
(In A Page: Pediatric Signs and Symptoms)

• Duchenne and Becker muscular dystrophy
• Spinal muscular atrophy
• Spinal cord disorders
  –Trauma
  –Myelitis
  –Neoplasm
  –AVM
  –Hemorrhage
  –Tansverse myelitis
• Limb-girdle myasthenia
• Dermatomyositis
• Congenital myopathies
  –Central core disease
  –Myotubular
  –Nemaline (rod)
  –Congenital fiber-type disproportion
• Facioscapulohumeral syndrome
• Limb-girdle muscular dystrophies
• Glycogen storage myopathies
• Endocrine myopathies
  –Hypo- and hyperthyroidism
  –Hyperparathyroidism
  –Adrenalism
• Polymyositis
• GM2 gangliosidosis
• Pompe disease
  –Glycogen storage disease type II
  –Acid maltase deficiency
• McArdle disease
• Carnitine deficiency
• Fatty acid oxidation defects
• Mitochondrial disorders
• Steroid-induced myopathy
• Slow channel syndrome
• Toxins
  –Organophosphates
  –Aminoglycosides
  –Tetrodotoxin (pufferfish)
• Conversion reaction
• Myasthenia gravis

Workup and Diagnosis

• History: Age upon reaching developmental milestones, abnormal gait, toe walking, easy fatigability, muscle cramps, facial weakness, cardiac, respiratory, GI problems, dark urine
• Physical exam: Muscle mass, texture and tenderness, scoliosis, cardiac exam, skin rashes, joint contractures
• Neurologic exam
  –Muscle strength and tone
  –Gowers sign
  –Mental status, eye movements
  –Facial movements, tongue fasciculations
  –Muscle stretch reflexes and sensory responses
  –Stance and gait
  –Spinal cord disorders, examine dermatomal sensory loss, anal wink, cremasteric reflex
• Labs: Muscle enzymes (CPK, aldolase); electrolytes, TSH, lactate, pyruvate, carnitine; ANA, RF, genetic testing for muscular dystrophy and spinal muscular atrophy; hexosaminidase, acetylcholine receptor antibodies, myoglobin in urine (muscle breakdown)
• EMG/nerve conduction studies
  –Differentiates dysfunction of the anterior horn cell, muscle, or neuromuscular junction
• Muscle biopsy for metabolic, inflammatory, and congenital myopathies; distinguishes myopathy from anterior horn cell disease
• MRI of the spine for spinal cord disorder
• Tensilon test for myasthenia

» READ BOOK EXCERPT ONLINE »

Source: In A Page: Pediatric Signs and Symptoms, 2007

Muscle Weakness – Distal: Differential Diagnosis
(In A Page: Pediatric Signs and Symptoms)

• Guillain-Barré syndrome (GBS)
  –Acute, acquired, or monophasic
  –Ascending weakness and parasthesias
• Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP)
• Compression neuropathy
  –Trauma
  –Neoplasm (e.g., plexiform neurofibroma in neurofibromatosis type 1)
• Charcot-Marie-Tooth
  –Defect in peripheral myelin protein
  –Causes distal segmental demyelination
  –Manifested by distal muscle atrophy and weakness
• Drug-induced
  –Phenytoin
  –Isoniazid
  –Nitrofurantoin
  –Vincristine
  –Zidovudine
• Spinal muscular atrophy
• Juvenile segmental spinal muscular atrophy
• Miller-Fisher syndrome
  –Clinical triad of ataxia, ophthalmoplegia, and areflexia
• Tick paralysis
• Juvenile amyotrophic lateral sclerosis
• Giant axonal neuropathy
• Vitamin B12 deficiency
• Toxic neuropathy
  –Arsenic
  –Lead
  –Mercury
  –Thallium
  –Glue sniffing
• Uremic neuropathy
• Idiopathic axonal neuropathy
• Hereditary distal myopathy
• Inclusion body myopathy
• Rheumatoid arthritis
• Refsum disease
• Metachromatic leukodystrophy
• Krabbe disease
• Cockayne syndrome
• Conversion reaction
  –Usually fluctuating and unpredictable

Workup and Diagnosis

• History
  –Acute vs chronic, associated sensory findings, associated systemic/neurologic abnormalities
  –Family history (family members may not be affected to same degree)
  –Toxic exposures
• Physical exam
  –Abnormal gait can be the presenting symptom of either proximal or distal leg weakness
  –Stumbling, especially with foot eversion or dorsiflexion
  –Weakness of the hand muscles (e.g., difficulty writing, opening jars, or working with tools)
  –Inspect muscle for atropy, hypertrophy, fasciculations, myotonia, cogwheeling
  –Palpate muscles for tenderness
  –Mirror movements, hypotonia, spasticity/rigidity
  –Assess strength and power with push/pull testing, functional hop in place, knee bends, posture
  –Pronator drift, standing on toes/heels, symmetry
  • Labs
    –Serum CK
    –In neuropathic disorders, CK is usually normal or mildly increased; moderate to severe elevation of CK suggests myopathy
  • Electromyogram/nerve conduction studies
    –Demonstrate the extent, chronicity, and categorization
  • Muscle biopsy
    –Histochemistry, EM, enzymatic/genetic testing

» READ BOOK EXCERPT ONLINE »

Source: In A Page: Pediatric Signs and Symptoms, 2007

ALKALOSIS (INCREASED PH): Approach to the Diagnosis
(Differential Diagnosis in Primary Care)

Taking a drug history and noting hyperventilation or vomiting during the clinical evaluation will assist in the diagnosis. Serial electrolytes, arterial blood gases, and drug screen are first-line laboratory tests to assist in the diagnosis.

» READ BOOK EXCERPT ONLINE »

Source: Differential Diagnosis in Primary Care, 2007

Weight gain, excessive: History and physical examination
(Handbook of Signs & Symptoms (Third Edition))

Determine your patient’s previous patterns of weight gain and loss. Does he have a family history of obesity, thyroid disease, or diabetes mellitus? Assess his eating and activity patterns. Has his appetite increased? Does he exercise regularly or at all? Next, ask about associated symptoms. Has he experienced visual disturbances, hoarseness, paresthesia, or increased urination and thirst? Has he become impotent? If the patient is female, has she had menstrual irregularities or experienced weight gain during menstruation?

Form an impression of the patient’s mental status. Is he anxious or depressed? Does he respond slowly? Is his memory poor? What medications is he using?

During your physical examination, measure skin-fold thickness to estimate fat reserves. (See Evaluating nutritional status, pages 644 and 645.) Note fat distribution and the presence of localized or generalized edema and overall nutritional status. Inspect for other abnormalities, such as abnormal body hair distribution or hair loss and dry skin. Take and record the patient’s vital signs.

» READ BOOK EXCERPT ONLINE »

Source: Handbook of Signs & Symptoms (Third Edition), 2006

Muscle weakness: History and physical examination
(Handbook of Signs & Symptoms (Third Edition))

Begin by determining the location of the patient’s muscle weakness. Ask if he has difficulty with specific movements such as rising from a chair. Find out when he first noticed the weakness; ask him whether it worsens with exercise or as the day progresses. Also ask about related symptoms, especially muscle or joint pain, altered sensory function, and fatigue.

Obtain a medical history, noting especially chronic disease, such as hyperthyroidism; musculoskeletal or neurologic problems, including recent trauma; a family history of chronic muscle weakness, especially in males; and alcohol and drug use.

Focus your physical examination on evaluating muscle strength. Test all major muscles bilaterally. (See Testing muscle strength, pages 418 and 419.) When testing, make sure that the patient’s effort is constant; if it isn’t, suspect pain or other reluctance to make the effort. If the patient complains of pain, ease or discontinue testing and have him try the movements again. Remember that the patient’s dominant arm, hand, and leg are somewhat stronger than their nondominant counterparts. Besides testing individual muscle strength, test for range of motion (ROM) at all major joints (shoulder, elbow, wrist, hip, knee, and ankle). Also test sensory function in the involved areas, and test deep tendon reflexes (DTRs) bilaterally.

» READ BOOK EXCERPT ONLINE »

Source: Handbook of Signs & Symptoms (Third Edition), 2006

Weight loss, excessive: History and physical examination
(Handbook of Signs & Symptoms (Third Edition))

Begin with a thorough diet history because weight loss almost always is caused by inadequate caloric intake. If the patient hasn’t been eating properly, try to determine why. Ask him about previous weight and if the recent loss was intentional. Be alert to lifestyle or occupational changes that may be a source of anxiety or depression. For example, has he gotten separated or divorced? Has a family member or friend died recently? Has he recently changed jobs?

Inquire about recent changes in bowel habits, such as diarrhea or bulky, floating stools. Has the patient had nausea, vomiting, or abdominal pain, which may indicate a GI disorder? Has he had excessive thirst, excessive urination, or heat intolerance, which may signal an endocrine disorder? Take a careful drug history, noting especially any use of diet pills and laxatives.

Carefully check the patient’s height and weight, and ask about his previous weight. Take his vital signs and note his general appearance: Is he well nourished? Do his clothes fit? Is muscle wasting evident? Ask about exact weight changes (with approximate dates).

Next, examine the patient’s skin for turgor and abnormal pigmentation, especially around the joints. Does he have pallor or jaundice? Examine his mouth, including the condition of his teeth or dentures. Look for signs of infection or irritation on the roof of the mouth, and note any hyperpigmentation of the buccal mucosa. Also, check the patient’s eyes for exophthalmos and his neck for swelling; evaluate his lungs for adventitious sounds. Inspect his abdomen for signs of wasting, and palpate for masses, tenderness, and an enlarged liver.

Conventional laboratory and radiologic investigations such as complete blood count, serum albumin levels, urinalysis, chest X-ray, and upper GI series usually reveal the cause. Almost all physical causes are clinically evident during the initial evaluation. Cancer, GI disorders, and depression are the most common pathologic causes.

» READ BOOK EXCERPT ONLINE »

Source: Handbook of Signs & Symptoms (Third Edition), 2006

Gait, steppage [Equine gait, paretic gait, prancing gait, weak gait]: History and physical examination
(Handbook of Signs & Symptoms (Third Edition))

Begin by asking the patient about the onset of the gait and recent changes in its character. Does a family member have a similar gait? Find out if the patient has had a traumatic injury to the buttocks, hips, legs, or knees. Ask about a history of chronic disorders that may be associated with polyneuropathy, such as diabetes mellitus, polyarteritis nodosa, and alcoholism. While you’re taking the history, observe whether the patient crosses his legs while sitting because this may put pressure on the peroneal nerve.

Inspect and palpate the patient’s calves and feet for muscle atrophy and wasting. Using a pin, test for sensory deficits along the entire length of both legs.

» READ BOOK EXCERPT ONLINE »

Source: Handbook of Signs & Symptoms (Third Edition), 2006

Hyperaldosteronism: Diagnosis
(Professional Guide to Diseases (Eighth Edition))

Persistently low serum potassium levels in a nonedematous patient who isn’t taking diuretics, who doesn’t have obvious GI losses (from vomiting or diarrhea), and who has a normal sodium intake, suggest hyperaldosteronism. If hypokalemia develops in a hypertensive patient shortly after starting treatment with potassium-wasting diuretics (such as thiazides), and if it persists after the diuretic has been discontinued and potassium replacement therapy has been instituted, evaluation for hyperaldosteronism is necessary.

CONFIRMING DIAGNOSIS A low plasma renin level that fails to increase appropriately during volume depletion (upright posture, sodium depletion) and a high plasma aldosterone level during volume expansion by salt loading confirm primary hyperaldosteronism in a hypertensive patient without edema.

The serum bicarbonate level is often elevated, with ensuing alkalosis due to hydrogen and potassium ion loss in the distal renal tubules. Other tests show markedly increased urinary aldosterone levels, increased plasma aldosterone levels and, in secondary hyperaldosteronism, increased plasma renin levels.

A suppression test is useful to differentiate between primary and secondary hyperaldosteronism. During this test, the patient receives oral desoxycorticosterone for 3 days while plasma aldosterone levels and urinary metabolites are continuously measured. These levels decrease in secondary hyperaldosteronism but remain the same in primary hyperaldosteronism. Simultaneously, renin levels are low in primary hyperaldosteronism and high in secondary hyperaldosteronism.

Other helpful diagnostic evidence includes an increase in plasma volume of 30% to 50% above normal, electrocardiogram signs of hypokalemia (ST-segment depression and U waves), chest X-ray showing left ventricular hypertrophy from chronic hypertension, and localization of the tumor by adrenal angiography or computed tomography scan.

» READ BOOK EXCERPT ONLINE »

Source: Professional Guide to Diseases (Eighth Edition), 2005

Weight gain, excessive: History and physical examination
(Professional Guide to Signs & Symptoms (Fifth Edition))

Determine your patient’s previous patterns of weight gain and loss. Does he have a family history of obesity, thyroid disease, or diabetes mellitus? Assess his eating and activity patterns. Has his appetite increased? Does he exercise regularly or at all? Next, ask about associated symptoms. Has he experienced visual disturbances, hoarseness, paresthesia, or increased urination and thirst? Has he become impotent? If the patient is female, has she had menstrual irregularities or experienced weight gain during menstruation?

Form an impression of the patient’s mental status. Is he anxious or depressed? Does he respond slowly? Is his memory poor? What medications is he using?

During your physical examination, measure skin-fold thickness to estimate fat reserves. (See Evaluating nutritional status.) Note fat distribution, the presence of localized or generalized edema, and overall nutritional status. Examine the patient for other abnormalities, such as abnormal body hair distribution or hair loss and dry skin. Take and record the patient’s vital signs.

» READ BOOK EXCERPT ONLINE »

Source: Professional Guide to Signs & Symptoms (Fifth Edition), 2006

Muscle weakness: History and physical examination
(Professional Guide to Signs & Symptoms (Fifth Edition))

Begin by determining the location of the patient’s muscle weakness. Ask if he has difficulty with specific movements, such as rising from a chair. Find out when he first noticed the weakness; ask him whether it worsens with exercise or as the day progresses. Also ask about related symptoms, especially muscle or joint pain, altered sensory function, and fatigue.

Obtain a medical history, noting especially chronic disease such as hyperthyroidism; musculoskeletal or neurologic problems, including recent trauma; family history of chronic muscle weakness, especially in males; and alcohol and drug use.

Focus your physical examination on evaluating muscle strength. Test all major muscles bilaterally. (See Testing muscle strength, pages 530 and 531.) When testing, make sure the patient’s effort is constant; if it isn’t, suspect pain or other reluctance to make the effort. If the patient complains of pain, ease or discontinue testing and have him try the movements again. Remember that the patient’s dominant arm, hand, and leg are somewhat stronger than their nondominant counterparts. Besides testing individual muscle strength, test for range of motion at all major joints (shoulder, elbow, wrist, hip, knee, and ankle). Also test sensory function in the involved areas, and test deep tendon reflexes bilaterally.

» READ BOOK EXCERPT ONLINE »

Source: Professional Guide to Signs & Symptoms (Fifth Edition), 2006

Weight loss, excessive: History and physical examination
(Professional Guide to Signs & Symptoms (Fifth Edition))

Begin with a thorough diet history because weight loss is almost always caused by inadequate caloric intake. If the patient hasn’t been eating properly, try to determine why. Ask about his previous weight and whether the recent loss was intentional. Be alert for lifestyle or occupational changes that may be causing anxiety or depression. For example, has he gotten separated or divorced? Has he recently changed jobs?

Inquire about recent changes in bowel habits, such as diarrhea or bulky, floating stools. Has the patient had nausea, vomiting, or abdominal pain, which may indicate a GI disorder? Has he had excessive thirst, excessive urination, or heat intolerance, which may signal an endocrine disorder? Take a careful drug history, noting especially the use of diet pills or laxatives.

Carefully check the patient’s height and weight, and ask about exact weight changes with approximate dates. Take his vital signs and note his general appearance: Is he well nourished? Do his clothes fit? Is muscle wasting evident?

Next, examine the patient’s skin for turgor and abnormal pigmentation, especially around the joints. Does he have pallor or jaundice? Examine his mouth, including the condition of his teeth or dentures. Look for signs of infection or irritation on the roof of the mouth, and note any hyperpigmentation of the buccal mucosa. Also, check the patient’s eyes for exophthalmos and his neck for swelling; auscultate his lungs for adventitious sounds. Inspect his abdomen for signs of wasting, and palpate for masses, tenderness, and an enlarged liver.

Conventional laboratory and radiologic tests, such as complete blood count, serum albumin levels, urinalysis, chest
X-rays, and upper GI series, usually reveal the cause. Almost all physical causes are clinically evident during the initial evaluation. Cancer, GI disorders, and depression are the most common pathologic causes.

» READ BOOK EXCERPT ONLINE »

Source: Professional Guide to Signs & Symptoms (Fifth Edition), 2006

Gait, steppage [Equine gait, paretic gait, prancing gait, weak gait]: History and physical examination
(Professional Guide to Signs & Symptoms (Fifth Edition))

Begin by asking the patient about the onset of the gait and any recent changes in its character. Does any family member have a similar gait? Find out if the patient has had any traumatic injury to the buttocks, hips, legs, or knees. Ask about a history of chronic disorders that may be associated with polyneuropathy, such as diabetes mellitus, polyarteritis nodosa, and alcoholism. While you’re taking the history, observe whether the patient crosses his legs while sitting because this may put pressure on the peroneal nerve.

Inspect and palpate the patient’s calves and feet for muscle atrophy and wasting. Using a pin, test for sensory deficits along the entire length of both legs.

» READ BOOK EXCERPT ONLINE »

Source: Professional Guide to Signs & Symptoms (Fifth Edition), 2006

Hyper-aldosteronism: Diagnosis
(Handbook of Diseases)

Persistently low serum potassium levels in a nonedematous patient who isn’t taking diuretics, doesn’t have obvious GI losses (from vomiting or diarrhea), and has a normal sodium intake suggest hyperaldosteronism.

If hypokalemia develops in a hypertensive patient shortly after starting treatment with potassium-wasting diuretics (such as thiazides), and if it persists after the diuretic has been discontinued and potassium replacement therapy has been instituted, evaluation for hyperaldosteronism is necessary.

A low plasma renin level that fails to increase appropriately during volume depletion (upright posture, sodium depletion) and a high plasma aldosterone level during volume expansion by salt loading confirm primary hyperaldosteronism in a hypertensive patient without edema.

The serum bicarbonate level is commonly elevated, with ensuing alkalosis due to hydrogen and potassium ion loss in the distal renal tubules.

Other tests show markedly increased urine aldosterone levels and increased plasma aldosterone levels. In secondary hyperaldosteronism, plasma renin levels are increased.

A suppression test is useful to differentiate between primary and secondary hyperaldosteronism. During this test, the patient receives desoxycorticosterone I.M. for 3 days while plasma aldosterone levels and urine metabolites are continuously measured. These levels decrease in secondary hyperaldosteronism but remain the same in primary hyperaldosteronism. Simultaneously, renin levels are low in primary hyperaldosteronism and high in secondary hyperaldosteronism.

Other findings include electrocardiogram signs of hypokalemia (ST-segment depression and flattened U waves), chest X-ray showing left ventricular hypertrophy from chronic hypertension, and localization of the tumor by adrenal angiography, computed tomography scans, or magnetic resonance imaging.

» READ BOOK EXCERPT ONLINE »

Source: Handbook of Diseases, 2003

Weight gain, excessive: History
(Signs & Symptoms: A 2-in-1 Reference for Nurses)

Determine your patient’s previous patterns of weight gain and loss. Does he have a family history of obesity, thyroid disease, or diabetes mellitus? Assess his eating and activity patterns. Has his appetite increased? Does he exercise regularly or at all? Next, ask about associated symptoms. Has he experienced vision disturbances, hoarseness, paresthesia, or increased urination and thirst? Has he become impotent? If the patient is female, has she had menstrual irregularities or experienced weight gain during menstruation?

Form an impression of the patient’s mental status. Is he anxious or depressed? Does he respond slowly? Is his memory poor? What medications is he using?

CULTURAL CUE:Body weight is influenced by gender and race. For example, Black men tend to weigh less than White men and Black women tend to weigh more than White women of the same age. Socioeconomic status also affects weight gain. Individuals of lower socioeconomic status tend to have more pronounced obesity than those of middle-class or upper middle-class status.

» READ BOOK EXCERPT ONLINE »

Source: Signs & Symptoms: A 2-in-1 Reference for Nurses, 2007

Muscle weakness: History
(Signs & Symptoms: A 2-in-1 Reference for Nurses)

Determine the location of the patient’s muscle weakness. Ask if he has difficulty with specific movements such as rising from a chair. Find out when he first noticed the weakness; ask him whether it worsens with exercise or as the day progresses. Also ask about related symptoms, especially muscle or joint pain, altered sensory function, and fatigue.

Obtain a medical history, noting especially chronic disease such as hyperthyroidism; musculoskeletal or neurologic problems, including recent trauma; family history of chronic muscle weakness, especially in males; and alcohol and drug use.

» READ BOOK EXCERPT ONLINE »

Source: Signs & Symptoms: A 2-in-1 Reference for Nurses, 2007

Weight loss, excessive: History
(Signs & Symptoms: A 2-in-1 Reference for Nurses)

Begin with a thorough diet history because weight loss almost always is caused by inadequate caloric intake. If the patient hasn’t been eating properly, try to determine why. Ask him about previous weight and if the recent loss was intentional. Be alert to lifestyle or occupational changes that may be a source of anxiety or depression. For example, has he gotten separated or divorced? Has he recently changed jobs?

Inquire about recent changes in bowel habits, such as diarrhea or bulky, floating stools. Has the patient had nausea, vomiting, or abdominal pain, which may indicate a GI disorder? Has he had excessive thirst, excessive urination, or heat intolerance, which may signal an endocrine disorder? Take a careful drug history, noting especially use of diet pills and laxatives.

» READ BOOK EXCERPT ONLINE »

Source: Signs & Symptoms: A 2-in-1 Reference for Nurses, 2007

Hypotonia and Weakness: Clinical Features and Diagnosis
(The Diagnostic Approach to Symptoms and Signs in Pediatrics)

Brain Disorders

Cerebral Malformations

Lissencephaly(smooth brain) causes marked hypotonia in neonatal period followed byseizures and global developmental delay. MRI is procedure of choiceto demonstrate malformations (see Chap.40, Microcephaly).

Zellweger syndrome, a peroxisomal disorder,is characterized by pachygyria, polymicrogyria, severe hypotonia,neonatal seizures, hepatomegaly, leukodystrophy, renal cysts, andstippled calcification of patellae (see Chap. 13, Developmental Delay).

Dandy-Walker malformation, which consistsof posterior fossa cyst contiguous with fourth ventricle, partialor complete absence of cerebellar vermis, and hydrocephalus maybe associated with hypotonia in early infancy.

Chromosomal Abnormalities

Hypotoniaand delayed motor development are constant features of trisomy 21.Other chromosomal abnormalities that may be associated with hypotoniainclude trisomy 20p, 4p–, 9p–, and 18q– syndromes.Chromosomal karyotype confirms diagnosis.

Severe hypotonia, poor feeding, weakcry, and diminished deep tendon reflexes may occur in neonatal periodwith Prader Willi syndrome. Clinical manifestations that appearin childhood include hyperphagia, obesity, impaired linear growth,and diminished cognitive function (see Chap. 44, Obesity).

Hypoxic-Ischemic Encephalopathy

Most common cause of hypotonia in newborns.May also occur after severe head trauma, intracranial hemorrhage,strangulation, suffocation, and near drowning.

Hypotonic Cerebral Palsy

May be suspected in children with historyof perinatal asphyxia or birth trauma. In many cases, cause is unknown.Clinical findings include hypotonia, delayed motor development,and sometimes athetosis and ataxia.

Intracranial Infection

Hypotonia may occur following bacterial meningitisor viral encephalitis (see Chap.3, Alteration in Consciousness).

Trauma

Head traumamay cause cerebral contusion and intracranial hemorrhage, whichcan produce focal neurologic deficits, including seizures and hemiparesis.

CT or MRI can confirm diagnosis.

Metabolic Disorders

A numberof metabolic disorders can cause hypotonia without significant weakness, includingamino acid (nonketotic hyperglycinemia), organic acid (propionic,isovaleric, and methylmalonic acidemias), and lysosomal storage(mucopolysaccharidoses, lipidoses) disorders (see Chap. 3, Alteration in Consciousness,and Chap. 13, Developmental Delay).

Screening tests include serum electrolytes,glucose, ammonia, amino acids, lactate, pyruvate, carnitine; andurinary ketones, organic acids, and mucopolysaccharides.

Neurodegenerative Disorders

Degenerativedisorders of CNS that cause hypotonia include

Gray matter diseases (Tay-Sachs disease,Alpers disease, Menkes disease, GM-1 gangliosidosis, GM-2 gangliosidosis)

White matter diseases (Canavan disease,Pelizaeus-Merzbacher disease)

Diseases of gray and white matter (Zellwegersyndrome, neonatal adrenoleukodystrophy, Leigh syndrome)

See Chap.13, Developmental Delay.

Nonspecific Mental Retardation

Hypotonia may be associated with nonspecificmental retardation. Other findings may include impaired or delayedmotor and language development.

Spinal Cord Disorders

Trauma

Spinal cordinjury secondary to trauma may cause hypotonia and weakness in acute phase.

Flaccid weakness occurs in lower extremitiesand sometimes upper extremities, depending on level of lesion. Deeptendon reflexes may be normal or hypoactive. Subsequently, hypotoniagives way to spasticity and tendon reflexes become hyperactive.

MRI is useful in defining locationand extent of injury.

Spinal Dysraphism

May be associatedwith hypotonia and weakness, usually of lower extremities.

Cutaneous dimples or tracts, subcutaneousmass, or abnormal collections of hair in spinal area should raisesuspicion of disorder of caudal neural tube formation. Sensory abnormalitiesof legs and feet and sphincter abnormalities also may be noted.

U/S may be performed initially.Combination of CT and MRI may be necessary for definitive diagnosis(see Chap. 69, Urinary Incontinence).

Neoplasm

Tumors affecting spinal cord may cause spinalpain with radiation to specific dermatome, extremity weakness, impairedsensation, and lack of bowel and bladder control (see Chap. 5, Back Pain).

Anterior Horn Cell Disorders

Spinal Muscular Atrophies

Affect anteriorhorn cells of spinal cord and lower motor nuclei of brainstem. Genetic transmissionmay be autosomal recessive (most common), autosomal dominant, orX-linked.

3 types of autosomal-recessive formshave been described. Genetic defect in these types involves q13region of chromosome 5.

Most severe is type I, with onset priorto 6 mos of age, failure to develop ability to sit, and death usuallyby 2 yrs of age. In type II, onset is before 18 mos of age, withfailure to develop ability to stand. Death occurs after 2 yrs ofage. Type III is defined by onset after 18 mos of age, with abilityto stand and usually walk, and death occurs in adulthood.

In type I, severe hypotonia and weaknessoccur, with legs more affected than arms, and proximal musculatureaffected more than distal.

Absence of deep tendon reflexes is almost alwaysfound.

Involvement of CN nuclei results indifficulty swallowing and weak cry.

Sensory and sphincter functions arenormal.

Muscle fasciculations may be seen,especially involving tongue.

Intelligence and language developmentare normal until regression begins to occur by about 1 yr of age.

Creatine phosphokinase (CPK) concentrationis normal.

U/S shows characteristic increasein intensity of echoes from muscle.

Fibrillation potentials may be seenwith electromyography. Motor nerve conduction velocities are normal.

Muscle biopsy shows characteristicdenervation pattern that helps confirm diagnosis. Molecular geneticanalysis is definitive.

Enteroviral Infection

Infectionwith enteroviruses can produce asymmetric weakness of limbs.

Prototype disease is poliomyelitis,but now only a few cases occur each year in the Western hemisphere,which are result of oral polio vaccine and not wild-type virus.Polioviruses (types 1, 2, 3) have predilection for anterior horncells of spinal cord and cranial nerve nuclei of brainstem.

Transmission is by fecal-oral route,with incubation period of 1–5 wks.

>90% of infectedchildren are asymptomatic or have mild nonparalytic disease.

Illness begins with URI or gastroenteritisfollowed within 1 wk by fever, headache, and muscle pain. Asymmetricextremity weakness (usually legs more than arms) and absence ofdeep tendon reflexes along with weakness of facial and pharyngealmuscles may occur.

Some children develop meningoencephalitiswith spinal fluid pleocytosis and increased protein concentration.

In most severe form, paralysis spreadsfrom legs to involve abdominal and thoracic musculature and arms.

Viral isolation from pharynx, stool,or spinal fluid is diagnostic. Specific polymerase chain reactiontests or paired serologic tests are also diagnostic.

Peripheral Nerve Disorders

Acute Inflammatory Demyelinating Polyradiculopathy (Guillain-Barré Syndrome)

Prototypedisorder for acute diffuse peripheral neuropathy. Thought to haveautoimmune basis, perhaps triggered by viral infection.

In typical cases, symmetric weaknessascends from legs to trunk to arms and finally to bulbar muscles.In mild cases, only legs may be affected.

Weakness may evolve over a few daysto a few weeks. Sensory symptoms and signs are mild with pain andloss of vibratory or position sense in some patients.

Loss of pain and touch sensation areless common.

Involvement of cranial motor nerves,most commonly facial nerve, may produce difficulty with swallowingand speech.

Respiratory impairment with decreasedvital capacity and hypercarbia or frank respiratory failure arecommon complications.

Involvement of autonomic nerves cancause life-threatening cardiac arrhythmias or fluctuations in BP.

CSF is often normal in first few daysof illness; however, CSF protein increases during first 2 wks andpeaks by 4–5 wks into illness. CSF WBC count is usually <10cells/mm³ but may be up to 50cells/mm³.

Electromyographic findings are consistentwith neurogenic abnormalities. Motor nerve conduction velocity isusually decreased.

Diagnosis is based on above findings.

Chronic Inflammatory Demyelinating Polyneuropathy

Thoughtto be immune mediated, but inciting stimulus is unknown.

Duration is >2 mos.

Clinical features include distal extremityweakness and sensory loss leading to gait disturbance. Deep tendonreflexes are hypoactive or absent. Cranial nerve involvement andpain are uncommon.

CSF protein concentration is increased,but CSF WBC count is normal.

Motor nerve conduction velocity isslow.

Sural nerve biopsy may show demyelinization.

Chronic Motor-Sensory Polyneuropathy

Chronicmotor-sensory neuropathies may be inherited or acquired.

Hereditary motor-sensory neuropathiestypes I and II are characterized by extremity weakness, foot deformities(pes cavus and hammer toes), and variable loss of sensation. Onsetis usually in first or second decade.

Type III is characterized by onsetduring first year of life, with hypotonia and delay in developmentalmilestones. Muscle weakness (proximal and distal) and absence ofdeep tendon reflexes occur in childhood.

Many other hereditary motor-sensoryneuropathies also have been described (Swaiman and Ashwal, 1999).All may be distinguished by clinical, electromyographic, nerve biopsy,and molecular genetic analysis findings.

Peripheral neuropathy is also a featureof other genetic disorders, including metachromatic leukodystrophy,globoid cell leukodystrophy, and Friedreich ataxia (see Chap. 4, Ataxia, and Chap. 13, Developmental Delay).

Toxic neuropathies include lead poisoningand use of the chemotherapeutic agent vincristine.

Sensory Neuropathies

Includecongenital sensory neuropathy and familial dysautonomia and maypresent in infancy or childhood.

Characterized by hypotonia, impairedor absence of deep tendon reflexes, occasional limb weakness, andautonomic phenomena (e.g., decreased lacrimation). Impaired pain,touch, and temperature sensation also occur.

Motor nerve conduction velocities arenormal, whereas sensory nerve responses are impaired.

Sural nerve biopsy helps distinguishcongenital sensory neuropathy from familial dysautonomia (see Chap. 66, Sweating).

Neuromuscular Junction Disorders

Myasthenia

Muscle weaknessstimulated by activity and relieved by rest characterizes myasthenia.

3 types are neonatal transient myastheniagravis, congenital myasthenic syndromes, and juvenile myastheniagravis.

Neonatal Transient Myasthenia Gravis

Autoimmunedisorder that occurs in small number of infants born to motherswith myasthenia gravis.

Thought that passive transfer of antibodydirected against fetal acetylcholine receptor protein from motherleads to decrease in available acetylcholine receptors at postsynapticmembrane.

Onset in most infants is within 24hrs of birth.

Clinical manifestations include generalizedhypotonia and weakness, feeding and respiratory difficulty, facialweakness, and occasionally ptosis.

Administration of anticholinesteraseagent (e.g., edrophonium chloride, which results in decreased ptosis)is diagnostic. Finding increased serum concentration of acetylcholinereceptor binding antibody is also diagnostic.

Congenital Myasthenic Syndromes

Caused bygenetic defects affecting neuromuscular junction and not by autoimmune process.Mothers do not have myasthenia gravis.

Most common of these disorders wasformerly called congenital myasthenia but now is referred to asend-plate acetylcholine receptor deficiency.

Onset is usually in first weeks oflife with ptosis.

Ophthalmoplegia appears in ensuingmonths. Only after significant activity do hypotonia and weaknessoccur.

Diagnosis may be made by observingresponse to anticholinesterase drugs. Electrophysiologic and alpha-bungarotoxinbinding studies confirm deficiency in number or function of acetylcholine receptors.

Juvenile Myasthenia Gravis

Classicor juvenile form of myasthenia gravis occurs in children >2yrs of age; however, onset is usually in adolescence.

Most cases are caused by decrease innumber of available acetylcholine receptors secondary to circulatingreceptor-binding antibodies.

Usual finding at any age is weaknessthat worsens with exercise or repetitive use of muscles.

Diagnosis can be confirmed by detectionof antibodies against acetylcholine receptor protein or by pharmacologicor electrophysiologic means. Repetitive stimulation of motor nerveproduces progressive decrease in amplitude of action potential (decrementalconduction).

Botulism

Neurotoxinproduced by C. botulinum impairs release of acetylcholine from cholinergicnerve terminals.

Illness may be acquired by ingestionof food that was contaminated with toxin or improperly preserved(food borne), contamination of wound by clostridium organisms (woundbotulism), or production of C. botulinum toxin in intestine afterexposure to spores (infant botulism).

Infant botulism is much more commonthan foodborne or wound botulism.

Onset is usually at 2–4 mos of age,although it can occur in neonatal period.

Initially poor feeding, constipation,hypotonia, and weakness occur. Illness progresses with impairedsucking and swallowing and more severe weakness during next fewdays. Ptosis is common finding, but extraocular function is usuallyintact. Pupillary reactions to light are impaired or absent.

Characteristic electromyogram showsincremental response of muscle action potential with repetitivenerve stimulation and frequent, brief-duration, small-amplitudemotor unit potentials.

Diagnosis is confirmed by isolationof organism or detection of toxin in stool.

Tick Paralysis

Neurotoxinsproduced by dog tick (D. variabilis), which is found primarily insoutheastern U.S., and by wood tick (D. andersoni), which is foundprimarily in Rocky Mountain states, prevent release of acetylcholineat neuromuscular junction.

Tick exposure usually begins 5–10days before onset of illness, which is characterized by acute ascendingflaccid paralysis similar to that seen with Guillain-Barré syndrome.

Deep tendon reflexes are decreasedor absent, and sensation is intact.

Finding tick, which is often on scalp,is diagnostic. Removal results in dramatic improvement.

Muscle Disorders

Primary clinical manifestation of muscledisease is weakness. Clinical presentation and course, mode of inheritance,muscle biopsy, and molecular genetic analysis help distinguish variousdisorders.

Congenital Myopathies

Central Core Disease

Onset ofthis autosomal-dominant disorder is in infancy or early childhood.

Gene locus has been mapped to chromosome19q13.1.

Usual presentation is hypotonia andweakness of proximal extremities (arms more than legs). Mild facialweakness also may occur.

Serum CPK is normal, and electromyographyusually shows myopathic pattern.

Muscle biopsy shows presence of coresof myofibrils undergoing degeneration in center of type I fibers.

Nemaline Rod Myopathy

2 formshave been described.

In more common autosomal-dominant form,gene locus has been mapped to chromosome 1, and in autosomal-recessiveform, to chromosome 2.

Onset of autosomal-dominant form isin childhood, with slowly progressive generalized weakness, whereasonset of autosomal-recessive form is in neonatal period with respiratoryinsufficiency or in infancy with hypotonia and delayed motor development.

Muscle biopsy shows distinctive rodlikebodies in muscle fibers.

Myotubular Myopathy

Genetictransmission is usually X-linked; however, milder autosomal-dominantand -recessive forms also exist.

Onset is usually in infancy, with generalizedhypotonia and weakness. Other findings include facial weakness,ptosis, and impaired extraocular movements.

Distinctive muscle biopsy shows musclefibers that resemble fetal myotubes.

Congenital Myopathy with Fiber-Type Disproportion

Genetictransmission may be autosomal dominant or autosomal recessive.

Onset is in infancy, with hypotoniaand weakness (proximal more than distal muscles). Facial weakness,congenital hip dislocation, and joint contractures also may occur.

Muscle biopsy shows predominance ofsmall type I fibers and compensatory hypertrophy of type II fibers.

Other

Several unusual congenital myopathies havebeen described with distinctive morphologic changes on muscle biopsy:fingerprint bodies, spheroid bodies, cytoplasmic bodies, sarcoplasmicbodies, zebra bodies, minicores, and Mallory body–likeinclusions.

Metabolic Myopathies

Glycogenoses

Glycogen Storage Disease Type II

Autosomal-recessivedisorder caused by deficiency of acid alpha-1,4-glucosidase (acidmaltase). Gene locus has been mapped to chromosome 17q25.2-q25.3.

Classic form (Pompe disease) presentsin infancy with severe hypotonia and weakness as well as difficultyin sucking and swallowing. Tongue is usually enlarged and may havefasciculations. Enlarged liver and cardiomyopathy are other usualfindings. Death usually occurs before 2 yrs of age.

Milder form may present in older childrenwith primarily skeletal muscle involvement.

Diagnosis may be confirmed by enzymeassay of muscle, or cultured fibroblasts, or by molecular geneticanalysis.

Glycogen Storage Disease Type III

Deficiencyof glycogen debrancher enzyme occurs in this autosomal-recessivedisorder. Gene locus has been mapped to chromosome 1p21. Involvementof both liver and muscle (type IIIa) is found in most affected individuals,whereas some have only liver involvement (type IIIb).

Characteristic findings include hypotonia,weakness, hepatomegaly, poor growth, hypoglycemia, and hyperlipidemia.

Enzyme assay of liver and muscle tissueconfirms diagnosis.

Carnitine Deficiency

Carnitine, produced almost exclusively inliver, is indispensable carrier of fatty acids into mitochondria,where they undergo beta oxidation. Most cases have been shown tobe due to defects in fatty acid oxidation; most common is medium-chainacyl-CoA dehydrogenase deficiency. 2 other disorders of carnitinemetabolism have been associated with decrease in carnitine concentrationin muscle: primary carnitine deficiency (carnitine transporter deficiency)and muscle carnitine deficiency.

Medium-Chain Acyl-CoA Dehydrogenase Deficiency

Autosomal-recessivedisorder caused by mutations in medium-chain acyl-CoA dehydrogenasegene, whose locus has been mapped to chromosome 1p31.

Presenting features are poor feeding,respiratory distress, hypotonia, and alteration in consciousness.

Lab findings include hypoglycemia withoutketones, metabolic acidosis, hyperammonemia, low serum carnitine,and dicarboxylic aciduria.

Assay of plasma acylcarnitines is diagnostic.Demonstration of enzyme defect in leukocytes or fibroblasts is definitive.

Primary Carnitine Deficiency (Carnitine Transporter Deficiency)

Caused bymutations in SLC22A5 gene on chromosome 5. This gene encodes sodium ion-dependentcarnitine transporter OCTN2.

Onset is usually in infancy or earlychildhood, with hypotonia and weakness. These individuals tend todevelop hypoglycemic coma precipitated by prolonged fasting.

Serum, muscle, and liver carnitineconcentrations are low.

Muscle Carnitine Deficiency

Autosomal-recessivedisorder that involves deficient transport of carnitine across intestinalmucosa.

Onset is usually in late childhoodor adolescence with generalized proximal muscle weakness.

Muscle biopsy reveals lipid storagemainly in type I fibers and low carnitine concentration in muscle.Serum carnitine concentration is normal.

Respiratory Chain Disorders

Includedefects in complex I, complex III, complex IV, and multiple enzymesof respiratory chain (mitochondrial DNA depletion).

Marked hypotonia and weakness may occurin neonatal period. Hepatomegaly and cardiomyopathy also may occur.Defects in complexes I, III, and IV also can present primarily asencephalopathy.

Abnormal serum lactate/pyruvateratio (>20) suggests respiratory chain disorder.

Muscle biopsy including electron microscopyand respiratory chain enzyme analysis is diagnostic.

Periodic Paralysis

3 typesof familial (genetic) periodic paralysis are hypokalemic, hyperkalemic,and normokalemic. Genetic transmission of each disorder is autosomal-dominant.

Hypokalemic periodic paralysis usuallypresents in childhood or adolescence with episodic weakness andlow serum potassium levels. Episodes may be precipitated by restafter exercise, meal high in carbohydrate content, exposure to cold,and physical or emotional stress. Gene locus has been mapped tochromosome 1q31-32.

Hyperkalemic periodic paralysis ismore likely to occur in infancy and childhood. Onset of episodicweakness usually occurs after exercise. Serum potassium concentrationis increased during an episode. Gene locus has been mapped to chromosome17q23.1-q25.3.

Normokalemic periodic paralysis isclinically similar to hyperkalemic form, but serum potassium concentrationis normal during an episode.

Endocrine Myopathies

Proximal extremity weakness (legs more thanarms) that is progressive can be caused by hyperthyroidism, hypothyroidism,hyperadrenalism, hypoadrenalism, hyperparathyroidism, and hypoparathyroidism.See other chapters for discussion of some of these disorders.

Dystrophies

Group of genetically transmitted muscle disorderscharacterized by progressive degeneration of skeletal muscle.

Congenital Muscular Dystrophy

Encompassesseveral disorders that are characterized by generalized hypotoniaand weakness and early joint contractures. Disorders can be classifiedaccording to presence of muscle involvement (merosin-positive congenitalmuscular dystrophy) or both muscle and CNS involvement [congenitalmuscular dystrophy with white matter abnormality (merosin-deficienttype), Fukuyama congenital muscular dystrophy, muscle-eye-braindisease, and Walker-Warburg syndrome].

Lab tests usually reveal increasedserum CPK, nonspecific myopathic pattern with electromyography,and dystrophic changes on muscle biopsy.

MRI demonstrates brain abnormalities.

Duchenne Muscular Dystrophy

This X-linkeddisorder is most common type of muscular dystrophy in childhood.

Caused by mutations in gene that encodesprotein dystrophin.

Onset is usually at 2–4 yrsof age with progressive muscle weakness, lumbar lordosis, calf musclepseudohypertrophy, and positive Gower sign. Cardiomyopathy and impairedintellectual ability also may occur.

Lab tests reveal very high serum CPK,increase in echoes of involved muscle on U/S, myopathicchanges on electromyography, and myofiber degeneration and connectivetissue proliferation on muscle biopsy.

Molecular genetic analysis is now standardfor diagnosis.

Becker Muscular Dystrophy

Same geneis defective in Becker muscular dystrophy as in Duchenne musculardystrophy, but in Becker muscular dystrophy onset is later in childhood(after 5 yrs of age), clinical course is milder, and progressionis slower.

Dystrophin analysis of muscle can distinguishDuchenne muscular dystrophy from Becker muscular dystrophy. In theformer, dystrophin content is <3% of normal, whereasin the latter, it is 3–20% of normal.

Emery-Dreifuss Muscular Dystrophy

2 typeshave been described. Type 1 is X-linked and caused by mutationsin gene that encodes the protein emerin, while type 2 is autosomal-dominantwith mutations in gene on chromosome 1q21.2 that encodes the proteinlamin A/C.

Both types have same clinical phenotypewith onset at 5–15 yrs of age.

Characteristic features include weakness,primarily in legs and shoulder girdle, cardiomyopathy, and normalintellectual function.

Serum CPK is mildly increased.

Molecular genetic analysis is definitive.

Limb-Girdle Muscular Dystrophy

Onset isin childhood or adolescence, with weakness of hip and shoulder girdlemuscles.

Later in the course, distal musclesbecome weak. Facial weakness may or may not occur.

Autosomal-dominant, autosomal-recessive,and X-linked transmission may occur depending on specific disorder.

Molecular genetic analysis is definitive.

Facioscapulohumeral Muscular Dystrophy

Autosomal-dominantdisorder associated with deletion at chromosome 4q35 locus.

Onset is variable but typically occursin second decade of life with weakness of facial, shoulder, andupper arm muscles. Foot extensor and pelvic girdle muscle weaknessmay also occur.

Serum CPK may be normal or increased.

Molecular genetic analysis is confirmatory.

Myotonic Syndromes: Myotonic Dystrophy

Autosomal-dominantdisorder almost always transmitted by affected mother. Abnormalgene has been mapped to chromosome 19q13 in most common form.

Mother usually has signs of myotonicdystrophy—long immobile face due to atrophy of temporalisand masseter muscles, ptosis, and myotonia (inability to open eyesfor a few seconds after closing them tightly and failure of immediateextension of fingers after forming clenched fist).

Usual findings in affected infant duringfirst days of life are hypotonia, bilateral facial weakness, poorfeeding, and respiratory difficulty.

Clinical findings of infant and motherand characteristic electromyogram in mother (motor unit potentialsthat wax and wane in amplitude and frequency indicative of myotonia)confirm diagnosis.

Beyond neonatal period, onset is usuallyduring adolescence or later.

Characterized by distal muscle weakness, especiallyof intrinsic muscles of hands, facial weakness with muscle atrophy,and myotonia (usually present after 5 yrs of age). Weakness is slowly progressiveand eventually involves proximal musculature.

Serum CPK is normal or mildly increased.Clinical features, family history, and characteristic electromyogramare diagnostic.

Molecular genetic analysis is definitive.

Inflammatory Myopathies

Dermatomyositis

This formof connective tissue disease has 3 main features: muscle weakness,skin lesions, and systemic symptoms (e.g., malaise and fatigue).

Usually occurs in school age children.

Weakness is usually proximal and symmetricand begins in legs, but some children have generalized weakness.Erythematous discoloration may be found over upper eyelids, nose,cheek, and joints (metacarpophalangeal, interphalangeal, elbow,knee). Gottron nodules also may be seen over finger joints. Othermanifestations include fever, swallowing difficulty, hepatosplenomegaly,lymphadenopathy, and calcinosis of muscle or skin.

Muscle biopsy helps confirm diagnosis.

Polymyositis

Producessymmetric weakness of proximal limb and trunk muscles without skinlesions but is uncommon in children.

Onset is usually insidious but progressiveover weeks or months.

Febrile illness occasionally precedesmuscle weakness.

Serum concentrations of muscle enzymes(creatine phosphokinase, aldolase, aspartate aminotransferase) areusually increased.

Muscle biopsy confirms diagnosis.

Connective Tissue Disorders

Congenital Laxity of Ligaments

Individualshave hypotonia and increased joint mobility but normal muscle strength andpreserved deep tendon reflexes.

Criteria of joint laxity and hypermobilityare hyperextension of knees and elbows beyond 180 degrees, increasedhip abduction (usually to 90 degrees), hyperextension of metacarpophalangeal jointsof fingers with extension of wrist to 90 degrees, approximationof thumb to anterior aspect of forearm, and dorsiflexion of anklesbeyond 45 degrees from neutral position.

Congenital dislocation of hip and scoliosismay be associated findings.

Ehlers-Danlos Syndrome

Primary manifestations are fragile, easilybruised, stretched skin, and hyperextensible joints. See Chap. 52, Purpura and Bleeding.

Marfan Syndrome

Easily stretched skin, hypermobile joints,long thin extremities and fingers, dislocated lens, and aortic incompetencecharacterize Marfan syndrome, an autosomal-dominant disorder. See Chap. 68, Tall Stature.

Metabolic Disorders

Hypotonia also may occur with hypopituitarism,renal tubular acidosis, rickets, and hypercalcemia. See discussionof some of these disorders in other chapters.

Diagnostic Approach

First stepis to determine whether disorder involves nervous system includingneuromuscular system. This can usually be accomplished by historyand physical exam.

If disorder involves nervous system,next step is to define anatomic level of abnormality—brain,spinal cord, anterior horn cell, peripheral nerve, neuromuscularjunction, or muscle. This can usually be accomplished by consideringdistinguishing features (e.g., pattern of weakness, deep tendonreflexes, presence of sensory loss or fasciculations, serum muscleenzyme levels, CSF findings, electromyographic pattern, nerve conductionvelocities, and muscle biopsy).

Final step is to make specific diagnosis,which usually can be done by analysis of the above findings, otherclinical findings, and other investigations.

Brain

Characteristicfindings with brain disorders include weakness of extremities (proximalas much as or more than distal), normal or increased deep tendonreflexes, seizures, developmental delay, and cognitive change.

Degree of weakness is usually lessstriking than degree of hypotonia. Cranial nerve nuclei also maybe involved.

Serum muscle enzymes, electromyography,and muscle biopsy are normal, except for particular disorders (e.g.,congenital muscle dystrophies) in which muscle and brain may beabnormal.

Neuroimaging is useful in diagnosisof many of these disorders.

Spinal Cord

Disordersaffecting spinal cord may produce flaccid weakness of all extremitiesif injury involves cervical region; usually normal or hypoactivedeep tendon reflexes, which can become hyperactive in next few weeksor months; sphincter abnormalities; and sensory level on trunk.

Cranial nerve function is normal.

MRI is useful in defining locationand extent of spinal cord lesion.

Anterior Horn Cell

Characteristicfindings of spinal muscular atrophies include severe hypotonia and weakness(proximal as much as or more than distal), muscle fasciculations,and absence of deep tendon reflexes. Facial weakness also may occur.Sensory function, spinal fluid analysis, and serum muscle enzymelevels are normal.

Fibrillations can be demonstrated byelectromyography.

Muscle biopsy shows denervation patternin which hallmark is atrophy of group of muscle fibers. Enteroviralinfection affecting anterior horn cells commonly produces asymmetricweakness and abnormal spinal fluid.

Peripheral Nerve

Characterizedby marked weakness (usually distal more than proximal), decreasedor absent deep tendon reflexes, abnormal sensory examination, increasedcerebrospinal fluid protein concentration, and decreased nerve conductionvelocities.

Muscle biopsy shows denervation pattern,and nerve biopsy is usually abnormal.

Neuromuscular Junction

Disordersof neuromuscular junction produce generalized weakness (proximalas much as distal). Facial weakness is usual finding, and extraocularmuscles may be involved. Deep tendon reflexes are usually normal.Sensory function, spinal fluid analysis, serum muscle enzyme levels,and muscle biopsy are normal.

Electromyography shows characteristicdecremental response to repetitive stimulation with myasthenia gravis.There is usually positive response to neostigmine or edrophonium.

Typical electromyographic findingsin botulism are incremental response with repetitive stimulationand frequent, brief duration, small amplitude motor unit potentials.Pupillary responses to light are impaired or absent with botulism.

Muscle

Muscle disordersproduce weakness, with proximal weakness often more pronounced thandistal weakness. Facial weakness is variable but may occur withseveral muscle disorders. These include central core disease, myotubularmyopathy, nemaline myopathy, congenital fiber disproportion, congenitalmuscular dystrophy, facioscapulohumeral dystrophy, and myotonicdystrophy. Deep tendon reflexes are usually decreased in proportionto weakness.

Sensory function and spinal fluid analysisare normal. Increased serum concentration of muscle enzymes is variable.

Electromyography shows small-amplitude,short-duration motor unit potentials and myopathic polyphasic potentials.

Muscle biopsy shows myopathic pattern,and nongrouped atrophy is essential feature.

Various studies of muscle (histologic,histochemical, biochemical, immunocytochemical, electron microscopic)are often needed for diagnosis.

Molecular genetic analysis can nowbe performed for definitive diagnosis of many muscle disorders.

>>

» READ BOOK EXCERPT ONLINE »

Source: The Diagnostic Approach to Symptoms and Signs in Pediatrics, 2006

Weight gain, excessive: History and physical examination
(Nursing: Interpreting Signs and Symptoms)

Determine your patient's previous patterns of weight gain and loss. Does he have a family history of obesity, thyroid disease, or diabetes mellitus? Assess his eating and activity patterns. Has his appetite increased? Does he exercise regularly or at all? Ask about associated symptoms. Has the patient experienced vision disturbances, hoarseness, paresthesia, or increased urination and thirst? Has he become impotent? If the patient is female, has she had menstrual irregularities or experienced weight gain during menstruation? Is she menopausal or postmenopausal?

Form an impression of the patient's mental status. Is he anxious or depressed? Does he respond slowly? Is his memory poor? What medications is he taking?

During your physical examination, measure skin-fold thickness to estimate fat reserves. (See Evaluating nutritional status, pages 644 and 645.) Note fat distribution and the presence of localized or generalized edema and overall nutritional status. Inspect for other abnormalities, such as abnormal body hair distribution or hair loss and dry skin. Take and record the patient's vital signs.

» READ BOOK EXCERPT ONLINE »

Source: Nursing: Interpreting Signs and Symptoms, 2007

Muscle weakness: History and physical examination
(Nursing: Interpreting Signs and Symptoms)

Begin by determining the location of the patient's muscle weakness. Ask if he has difficulty with specific movements such as rising from a chair. Find out when he first noticed the weakness; ask him whether it worsens with exercise or as the day progresses. Also ask about related symptoms, especially muscle or joint pain, altered sensory function, and fatigue.

Obtain a medical history, noting especially chronic disease, such as hyperthyroidism; musculoskeletal or neurologic problems, including recent trauma; a family history of chronic muscle weakness, especially in males; and alcohol and drug use.

Focus your physical examination on evaluating muscle strength. Test all major muscles bilaterally. (See Testing muscle strength, pages 410 and 411.) When testing, make sure that the patient's effort is constant; if it isn't, suspect pain or other reluctance to make the effort. If the patient complains of pain, ease or discontinue testing and have him try the movements again. Remember that the patient's dominant arm, hand, and leg are somewhat stronger than their nondominant counterparts. Besides testing individual muscle strength, test for range of motion (ROM) of all major joints (such as shoulder, elbow, wrist, hip, knee, and ankle). Also test sensory function in the involved areas, and test deep tendon reflexes (DTRs) bilaterally.

» READ BOOK EXCERPT ONLINE »

Source: Nursing: Interpreting Signs and Symptoms, 2007

Weight loss, excessive: History and physical examination
(Nursing: Interpreting Signs and Symptoms)

Begin with a thorough diet history because weight loss is almost always caused by inadequate caloric intake. If the patient hasn't been eating properly, try to determine why. Ask him about previous weight and whether the recent loss was intentional. Determine how long the weight loss has been taking place. Be alert to lifestyle or occupational changes that may be a source of anxiety or depression. Has the patient recently experienced a loss?

Inquire about recent changes in bowel habits, such as diarrhea or bulky, floating stools. Has the patient had nausea, vomiting, or abdominal pain, which may indicate a GI disorder? Has he had excessive thirst, excessive urination, or heat intolerance, which may signal an endocrine disorder? Has he been experiencing other pain? If so, ask about the location of the pain and how long he has had it. Take a careful drug history, noting especially use of diet pills and laxatives.

Carefully check the patient's height and weight and ask about his previous weight. Take his vital signs and note his general appearance: Is he well nourished? Do his clothes fit? Is muscle wasting evident? Ask about exact weight changes (with approximate dates).

Examine the patient's skin for turgor and abnormal pigmentation, especially around the joints. Does he have pallor or jaundice? Examine his mouth, including the condition of his teeth or dentures. Look for signs of infection or irritation on the roof of the mouth and note hyperpigmentation of the buccal mucosa. Check the patient's eyes for exophthalmos and his neck for swelling; evaluate his lungs for adventitious sounds. Inspect his abdomen for signs of wasting, and palpate for masses, tenderness, and an enlarged liver.

Conventional laboratory and radiologic investigations such as complete blood count, serum albumin levels, urinalysis, chest X-ray, and upper GI series usually reveal the cause. Almost all physical causes are clinically evident during the initial evaluation. Cancer, GI disorders, and depression are the most common pathologic causes.

» READ BOOK EXCERPT ONLINE »

Source: Nursing: Interpreting Signs and Symptoms, 2007

Gait, steppage [Equine gait, paretic gait, prancing gait, weak gait]: History and physical examination
(Nursing: Interpreting Signs and Symptoms)

Begin by asking the patient about the onset of the gait and recent changes in its character. Does a family member have a similar gait? Find out if the patient has had a traumatic injury to the buttocks, hips, legs, or knees. Ask about a history of chronic disorders that may be associated with polyneuropathy, such as diabetes mellitus, polyarteritis nodosa, and alcoholism. While you're taking the history, observe whether the patient crosses his legs while sitting because this may put pressure on the peroneal nerve.

Inspect and palpate the patient's calves and feet for muscle atrophy and wasting. Using a pin, test for sensory deficits along the entire length of both legs.

» READ BOOK EXCERPT ONLINE »

Source: Nursing: Interpreting Signs and Symptoms, 2007

ALKALOSIS (INCREASED pH): Approach to the Diagnosis
(Differential Diagnosis in Primary Care)

Taking a drug history and noting hyperventilation or vomiting during the clinical evaluation will assist in the diagnosis. Serial electrolytes, arterial blood gases, and drug screen are first-line laboratory tests to assist in the diagnosis.

» READ BOOK EXCERPT ONLINE »

Source: Differential Diagnosis in Primary Care, 2007

 » Next page: Signs of Primary Hyperaldosteronism

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