Differential Diagnosis in Neurology

12.13. Myopathy of Infectious Disease

Viral Myositis

• General features:
  • Not immune mediated
  • Early cellular changes precede an inflammatory response
  • Immunosuppression does not prevent viral associated muscle damage

Epidemic Pleurodynia (Bornholm disease)

• General Features:
  • Usually caused by group B coxsackie virus; rarely group A or echovirus
• Clinical Presentation:
  • Abrupt onset in 75% of patients
  • May have prodrome of headache, anorexia and muscle hyperalgesia for up to ten days
  • Deep breathing, valsalva maneuvers or cough causes chest pain
  • Headache, fever, anorexia, cough and nausea and vomiting are common
  • Lasts for 2 to 14 days
  • Associated sequelae:
    • Orchitis
    • Aseptic meningitis
    • Pericarditis
• Laboratory evaluation:
  • Routine CBC, liver function tests are normal
• Pathology (muscle biopsy):
  • Rare inflammatory changes noted with muscle biopsy

Benign Acute Childhood Myositis

• General Features:
  • Myositis in a small minority of affected children
  • Influenza B virus in greater than 50%; influenza A in 10%; small number of patients with parainfluenza and adenovirus
  • Adults rarely affected
• Clinical Presentation:
  • Occurs during epidemic of influenza
  • Young boys affected (mean nine years of age)
  • Initiated 4–5 days following upper respiratory infection
  • Severe calf tenderness and pain; duration of 4–10 days; slight swelling
  • Recurrent myositis may occur from a different strain
• Laboratory Evaluation:
  • Normal sed rate
  • Moderately elevated CK; severe patients may demonstrate SGOT and LDH elevation
• EMG:
  • Myopathic MUAPs; calves most prominent, but upper extremities can be involved

Acute Viral Myositis

• General features:
  • May occur during epidemics
  • Adults are more severely affected than children
  • Myalgia is common during viral infection:
    • Cytokines IL-1, IL-6 and TNF-α are increased
• Clinical presentation:
  • Acute onset
  • Myalgia
  • Fever
  • Myoglobinuria
  • Swelling
  • Associated findings in severe patients:
    • Myocarditis
    • Renal failure
    • Pneumonia
  • Weakness recovers within 2–3 weeks
  • Epidemic benign myalgia of the neck (influenza)
• Laboratory Evaluation:
  • Elevated CK (highest with associated myoglobinuria)
  • 50% of patients have elevated ESR
  • Increased BUN and Creatinine occurs with the myoglobinuria
• Pathology (muscle biopsy):
  • Myositis with necrosis and perivascular and interstitial inflammation
  • Focal changes

Myopathy of HIV

• General features:
  • Occurs primarily with late infection
  • Probably a cell mediated autoimmune response
• Clinical presentation:
  • Subacute or slowly progressive inflammatory myopathy throughout the course of the illness
  • Usually in late stage of HIV; may be seen with acute infection
  • Symmetrical proximal muscle weakness
  • Myalgia
  • Rarely an acute onset with myocardial and swallowing involvement
  • Associated with dementia and peripheral neuropathy
• Laboratory evaluation:
  • Elevated CK (10–15 times normal)
  • Myoglobinuria is rare
• EMG:
  • Low amplitude and brief MUAPs; positive sharp waves; fibrillation potentials
• Pathology (muscle biopsy):
  • Inflammatory macrophages and CD8+ cytotoxic infiltrates that are perimysial, endomysial and perivascular
  • Invasion of both necrotic and non-necrotic muscle fibers
  • Nemaline rods may be found in muscle fibers (usually with AZT myopathy)

Opportunistic Infections of Muscle in HIV Patients

• Myobacterium tuberculosis
• Mycobacterium avium intracellular
• Cryptococcus
• Pyomyositis:
  • Staphylococcus aureus most common
  • Salmonella (10%)
  • Streptococcus (4%)

HTLV-1 Myositis

• General Features:
  • Causes T-cell leukemia, polymyositis and tropical spastic paraparesis
  • Transmitted by blood products and sexual contact
  • Endemic in Kii peninsula of Japan, parts of South America, the Caribbean Islands and Central Africa
  • May coexist with HIV and causes spastic paraparesis
  • Less prevalent polymyositis than spastic paraparesis with HTLV–1 infection in Japan
  • Possible T-cell mediated inflammatory reaction; MHC-I restricted cytotoxic process
• Clinical Presentation:
  • May occur in isolation or with T-cell leukemia and spastic paraparesis
  • Slowly progressive proximal myopathy
  • Proximal muscle and neck flexor weakness
• Laboratory Evaluation:
  • CK elevated
• EMG:
  • Myopathic
  • Fibrillation potentials
• Pathology (muscle biopsy):
  • Inflammatory myopathic changes similar to HIV myopathy

Leptospirosis

• General Features:
  • Leptospira interrogans is the major genus causing clinical disease; a gram negative rod
  • Reported in all regions of the USA
  • Infection in man is incidental; infected animal hosts (rats, skunks, opossum, domestic animals) shed leptospira in urine. Infection in man occurs due to contact with animals or through contaminated soil or water
• Clinical Presentation:
  • Occurs in all age groups; primarily a disease of children and young adults
  • Immersion in contaminated water is common source of infection
  • Hepatic, renal and muscle involvement
  • Myalgias of major muscles
  • Concomitant liver involvement with jaundice
  • Associated meningitis, liver, heart and renal involvement
• Laboratory evaluation:
  • Early stage has neutrophilia; rare thrombocytopenia
  • 50% of patients demonstrate an elevated sed rate
  • Elevated CPK
  • Leptospira excreted in the urine
  • Serologic tests are positive
• Pathology (muscle biopsy):
  • Swelling, vacuolation and hyalination

Fungal Myositis

• General Features:
  • Occurs in immunocompromised patients
  • Organisms:
    • Candida (most common)
    • Disseminated infection with muscle involvement from:
      • Cryptococcus
      • Aspergillus
      • Sporotrichia
      • Actinomyces
      • Histoplasma
    • Cryptococcus

Candida

• Clinical Presentation:
  • Immunocompromised host or in the setting of prolonged use of broad spectrum antibiotics
  • High fever
  • Erythematous skin rash
  • Severe myalgia and muscle tenderness
  • Lower extremities are involved, more severely than upper extremities
• Muscle biopsy:
  • Hemorrhagic necrosis and budding yeast, pseudohyphae and inflammatory cells.

Tuberculous Myositis 

• General features:
  • Granulomatous myositis
  • Species involved:
    • Mycobacterium tuberculosis
    • M. Ulcerans
    • M. fortuitum
    • M. cholinate
    • M. haemophilum
    • M. xenopi
• Clinical presentation:
  • Immunocompromised patients
  • Spreads from infected foci
  • Single or multiple abscesses
  • Hematogenous spread is rare
  • Enlarged muscle masses; involvement of adjacent lymph nodes
• Pathology (muscle biopsy):
  • Granulomatous inflammation; histiocytes and macrophages surround an area of caseation
  • Acid fast bacilli noted in the lesions

Sarcoid 

• General features:
  • Incidence higher in black than white patients
  • Patients with sarcoid have up to 60% incidence of muscle involvement
  • Associated involvement of CNS (dura, posterior hypothalamus, pituitary, optic chiasm and parenchyma); lungs, heart, skin (erythema nodosa); uveitis
• Clinical presentation:
  • Muscle involvement is most often asymptomatic
  • Acute myositis is rare
  • Painful proximal muscle weakness; rare cramps and contracture
  • Rare dysphagia, ocular muscle involvement and respiratory compromise
  • Mass in a muscle
  • Chronic sarcoid myopathy evolves into proximal wasting and weakness
  • Usually an associated neuropathy
• Laboratory Evaluation:
  • Chest X-ray is positive in 90% of patients; demonstrates hilar adenopathy or an interstitial pattern
  • Elevated ACE levels (angiotensin converting enzyme)
  • MRI of muscle:
    • Distinctive star-shaped pattern with peripheral gadolinium enhancement
• EMG:
  • Myopathic; often associated neuropathic features from the concomitant neuropathy
• Pathology (muscle biopsy):
  • Granulomatous inflammation of surrounding perifascicular connective tissue
  • Necrosis of individual muscle fibers is rare

Lyme Disease 

• General Features:
  • Organism is Borrelia burgdorferi (spirochete)
  • Deer tick is the usual transmitting host; carried also by dogs, but not cats
• Clinical Presentation:
  • Associated rash (erythema marginatum); early flu-like symptoms followed by migratory arthritis, neurologic and cardiac involvement
  • Myalgia occurs in the chronic phase; orbital myositis is a rare manifestation
• Laboratory Evaluation:
  • PCR of CSF and blood most helpful after screen for serum antibodies
• Pathology (muscle biopsy):
  • Lymphocytic and mononuclear inflammatory cell invasion of muscle
  • Spirochetes seen in muscle fibers

Trichinosis 

• General Features:
  • Trichinella spiralis is the organism
  • Usually contracted by eating raw or inadequately cooked pork products
  • Pigs eat infected rats; humans eat pork muscle containing encysted larvae that encyst in the small intestine and develop into adults in its mucosa. Five days after infection, females deposit larvae that migrate through tissue to encyst. Larvae encystation in muscle may continue for two weeks. Larvae become calcified.
  • Bear or wolf meat may contain larvae
• Clinical Presentation:
  • Incubation period after eating pseudocysts is 2–12 days
  • Abdominal pain and diarrhea followed by fever and myalgia (primarily in proximal muscle) is concurrent with infestation
  • Periorbital swelling and edema is common
  • Acute proximal myopathy can occur; extraocular, intercostal and diaphragmatic muscles may be involved
  • Myocarditis and CNS involvement can be associated
• Laboratory evaluation:
  • Marked blood and CSF eosinophilia
  • CK is elevated
  • Serology for Trichinella antibodies is positive in 3–4 weeks
• EMG:
  • Myopathic MUAPs with fibrillations
• Pathology (muscle biopsy)
  • Pseudocysts with Trichinella larvae are seen

Cysticercosis 

• General Features:
  • Organism is Taenia solium
  • Oral route from under washed meat or unwashed vegetables
  • Mature larvae penetrates the intestinal mucosa (released from the ova by gastric acid) and is disseminated by the lymphatics and hematogenously
  • Larvae mature in 2–3 months (5–6 mm in length and 8–10 mm in width) and grow rapidly in infested tissues

• Clinical Presentation:
  • CNS manifestations predominate:
    • Seizures
    • Focal neurologic deficits
    • Racemose ventricular from with hydrocephalus
    • Meningoencephalitis
  • Muscle involvement:
    • Weakness
    • Hypertrophy (symmetric in limb girdles)
    • Pain
    • Nodular muscle involvement
    • Proptosis and ophthalmoparesis is seen
• Imaging Evaluation:
  • CT or MRI scanning demonstrate calcified cysts in brain and muscle
• Pathology:
  • Cysticerci are identified

Cestodes (Tapeworms) 

• General Features:
  • Spirometra: cestodes that can involve muscle
    • Tapeworms:
      • Spirometra
      • Echinococcus
      • Spirometra mansonoides is the dog and cat tapeworm; may accidentally infect humans
  • Infective stage:
    • Second stage larvae (sparganum) gains access to the host by oral route or through open wounds
    • Encysts in subcutaneous tissue and muscle; also less frequently in viscera or the eye
• Clinical presentation:
  • Slowly enlarging subcutaneous nodule in muscle or skin; may migrate distally
• Pathology (muscle biopsy):
  • Sparganum is detected in the nodule

Echinococcus 

• General features:
  • Clinically relevant species to man are Echinococcus granulosa and Echinococcus multilocularis
  • Cause infection in dogs and wolves; infection in human is hydatoids caused by ingestion of contaminated food
• Clinical presentation:
  • Lobular cyst in the muscle (hydatid cyst); may grow and calcify; not painful
• Laboratory evaluation
  • Serology is positive

Rare Nematodes that can Infect Muscle 

• General Features:
  • Toxocara canis (T. coli)
  • Ancylostoma canium (cutaneous larva migrans)
  • Dracunculus medinensis (Africa, India and the Middle East)
• Clinical Presentation:
  • Toxocara usually causes visceral larvae migrans in children
  • Patients may be asymptomatic with eosinophilia alone
  • Myalgia in association with fever, hepatosplenomegaly, pneumonitis, ocular invasion and meningoencephalitis in severe cases
• Pathology (muscle biopsy)
  • Granulomatous inflammation

Protozoan Muscle Infection 

• General features:
  • Usual organisms are toxoplasma, sarcocystis, and trypanosoma
  • Malaria (muscle necrosis and myoglobinuria)

Toxoplasmosis 

• General features:
  • Toxoplasma gondii is the organism
  • Immunocompromised patients
  • Transmission to humans occurs most commonly from cat feces or undercooked meat; placenta and blood products
  • Dissemination occurs from tachyzoites that penetrate leukocytes and are hematogenous
• Clinical Presentation:
  • Subacute polymyositis with associated fever and proximal weakness
  • Associated lymphadenopathy
• Laboratory Evaluation:
  • Elevated muscle enzymes
  • Increased immunoglobulin IgM (positive serology)
  • Isolation of toxoplasma from body fluid
• EMG:
  • Myopathic MUAP; typical of inflammatory myopathy
• Pathology (muscle biopsy):
  • Histiocytes and lymphocytes in the peri and endomysium; Toxoplasma cysts
  • Giant cells in inflammatory aggregates