Tag Archives: Muscle

Necrotizing Autoimmune Myopathy NAM

Diagnosis: Clinical features plus positive antibodies and usually with necrotizing myopathy on biopsy Clinical features: Age range 30-60, progressive myopathy with profound proximal muscle weakness. May also occur in patients recieving statins, but most patients are statin naive Antibodies: Positive antibodies Anti-HMGCR Abs (3-Hydroxy-3-Methylglutaryl-Coenzyme A Reductase) Muscle biopsy: H&E: Necrotic fibers with a few regenerating … Continue reading Necrotizing Autoimmune Myopathy NAM →

Mitochondrial Neurogastrointestinal Encephalomyopathy MNGIE

Synonyms: a.k.a. MINGE, rare Diagnosis: Genetic analysis Genetics: POLG gene or Thymidine phosphorylase (TP) mutation TP mutation: Autosomal recessive Mitochondrial DNA (mtDNA) analysis: depletion, deletions, and point mutation Clinical features: External ophthalmoplegia, gastrointestinal dysmotility (dysphagia and intestinal pseudoobstruction) and pain, cachexia, peripheral neuropathy, encephalopathy Findings on investigations: MRI: leukoencephalopathy Muscle biopsy: ragged red fibres Treatment: … Continue reading Mitochondrial Neurogastrointestinal Encephalomyopathy MNGIE →

Kearns-Sayre Syndrome KSS

Clinical features: Onset before 20 years of age. Progressive external opthalmoplegia (restricted eye movements, usually movements are not dysconjugated) and pigmentory retinopathy. Also myopathy, heart block, CNS deficits, short stature. Pathology: Muscle biopsy: Gomori trichrome: Ragged red fibres Variation in muscle size COX negative fibres Brainstem and cerebellum: neuronal loss. Spongy to vacuolar myelinopathy. May … Continue reading Kearns-Sayre Syndrome KSS →

Mitochondrial Disorders

There are many diseases that are included in mitochondrial disorders. They often share common features. Synonyms: a.k.a. mitochondrial cytopathies, mitochondrial neurological disorders Subtypes of mitochondrial disorders: Alper syndrome a.k.a. Alper-Huttenlocher syndrome a.k.a. progressive infantile poliodystrophy Kearns-Sayre Syndrome KSS Mitochondrial encephalomyopathy lactic acidosis and stroke MELAS Myoclonic epilepsy and ragged red fibres MERRF Mitochondrial neurogastrointestinal encephalomyopathy … Continue reading Mitochondrial Disorders →

Lipid Storage diseases

Lipide storage myopathies: Carnitine deficiency Carnitine palmityl transferase II deficiency   Carnitine deficiency: Diagnosis: There are various forms: Muscle carnitine deficiency Systemic carnitine deficiency Secondary carnitine deficiency Muscle carnitine deficiency: Low muscle carnitine levels. Normal systemic carnitine levels Muscle biopsy: Vacuolar myopathy. Lipid droplets in type 1 fibres. Systemic carnitine deficiency: Systemic carnitine levels: low … Continue reading Lipid Storage diseases →

Myoadenylate Deaminase Deficiency MAD deficiency

Genetics: Autosomal recessive AMPD1 gene mutation chr. 1 Clinical features: Broad: childhood to late adulthood, myalgia induced by exercise to rhabdomyolysis Skeletal muscle only, non-progressive Muscle biopsy: MAD: no staining Treatment: D-Ribose P.O. Related articles: Myopathy,

Sporadic Late Onset Nemaline Myopathy SLONM

Synonyms: a.k.a. Adult from of nemalin myopathy a.k.a. acquired nemaline myopathy, rare: Clinical features: Adults a.k.a. late onset nemaline myopathy: usually >40 year olds, head drop, proximal >distal weakness, dysphagia, respiratory weakness, proximal and axial atrophy Associated conditions: SPEP: monoclonal gammopathy. HIV associated nemaline myopathy. Muscle biopsy: HE fibre atrophy without grouping, subsarcolemmal increased eosinophilic … Continue reading Sporadic Late Onset Nemaline Myopathy SLONM →

Condrodystrophic Myotonia

This is a very rare condition Synonyms: a.k.a. Schwartz-Jampil Syndrome SJS Clinical features: Myotonia +distichiasis (double row of eyelashes) Findings on investigations: EMG: Myotonia Genetics: Autosomal recessive Genetics: Perlecan gene mutation, HSPG2 gene chr. 1p35-p36.1 Related articles: Myopathy, Myotonic dystrophy DM1, Proximal myotonic myopathy (Myotonic dystrophy DM2), Myotonia Congenita (Thomsen’s disease)

Paramyotonia Congenita

Genetics: SCN4A 17q23 Clinical features: Myotonia (inability to relax) No improvement with exercise Precipitated by cold exposure. Flaccid paralysis may occur Related articles: Myopathy, Myotonic dystrophy DM1, Proximal myotonic myopathy (Myotonic dystrophy DM2), Myotonia Congenita (Thomsen’s disease)

Non-Dystrophic Myotonias

Diagnosis: Clinical features: childhood onset of myotonia +muscle hypertrophy There are multiple forms: Becker myotonia: Autosomal recessive Thomsen disease: (see appropriate section) Genetics: Autosomal dominant Genetic analysis: chloride channel CLCN1 gene mutations on chromosome 7. Different mutations for each. Muscle biopsy: Variation in fibre size. Rare centronucleation. Type 2A fibre hypertrophy. Type 2B fibres may … Continue reading Non-Dystrophic Myotonias →

Myotonia Congenita

A form of nondystrophic myotonia Synonyms: a.k.a. Thomsen’s disease Clinical features: 1st and 2nd decade When infant: inability to open eyes after face is washed, peculiar cry Muscular hypertrophy (generalized), myotonia (worse in cold), No weakness Warm up phenomenon: improved strength and movement after warm up Genetics: Autosomal dominant Genetic analysis: chloride channel CLCN1 gene mutations on … Continue reading Myotonia Congenita →

Proximal Myotonic Myopathy

Synonyms: a.k.a. myotonic dystrophy type 2 a.k.a. DM2 Diagnosis: The diagnosis is confirmed by genetic analysis Muscle biopsy: type 2 fibre atrophy, Genetics: Genetic analysis: CCTG repeat expansion in ZNF9 gene chromosome 3. Related articles: Myopathy, Myotonic dystrophy DM1,

Myotonic Dystrophy DM1

Synonyms: a.k.a. Dystrophia myotonica a.k.a. DM a.k.a. DM1 a.k.a. Steinert disease Diagnosis: Clinical +EMG +consistent labs Clinical features: Early frontal baldness, Wasting of temporalis (hatchet face), massester and sternocleidomastoid (swan neck), Ptosis, facial weakness. Weakness and atrophy of distal arms and finger flexors, and quadriceps and tibialis anterior (foot drop) Decreased reflexes Myotonia: difficulty releasing … Continue reading Myotonic Dystrophy DM1 →

Congenital Muscular Dystrophies CMD

These are a type of muscular dystrophy. Don’t confuse these diseases with non-dystrophic congenital myopathies. Merosin (Laminin 2) negative CMD: Clinical features: Cause hypotonia in the infant Pathology, Muscle or skin biopsy: H and E: dystrophic picture Immunohistochemistry: absent Mersonin (Laminin 2) in basement membrane. Findings on investigations: MRI: white matter changes   Merosin positive … Continue reading Congenital Muscular Dystrophies CMD →

Oculopharyngeal Dystrophy OPMD

Synonyms: a.k.a. oculopharyngeal muscular dystrophy OPMD Muscle biopsy: Rare rimmed vacuoles. Intranuclear inclusions. Occasionally type 1 fibre predominance and occasionally ragged red fibres Genetics: Autosomal dominant PABP2 gene, Chr. 14q11.2-q13, expanded trinucleotide repeat (polyalanine) GCG in PABP2 poly A binding nuclear protein 2. Clinical features: Ptosis, dysphagia Later on proximal limb weakness and gait abnormalities … Continue reading Oculopharyngeal Dystrophy OPMD →

Fascioscapulohumeral Myopathy FSH

Synonyms: a.k.a. Landuzy-Dejerine disease Muscle biopsy: 3 patterns Pseudoneurogenic: atrophied angulated fibres in nests Dystrophic: whorled fibres, moth eaten fibres, lobulated fibres. Endomysial fibrosis. Pseudomyositic: inflammatory cellular mononuclear infiltrates Diagnosis: Genetic analysis (blood test): deletion at 4q35. i.e. deletion of the telomeric region Genetics: Genetic analysis (blood test): deletion at 4q35. i.e. deletion of the … Continue reading Fascioscapulohumeral Myopathy FSH →

Emery-Dreifuss Muscular Dystrophy

Synonyms: a.k.a. Humeroperoneal dystrophy Genetics: X linked recessive Clinical features: Weakness in biceps, triceps, distal leg muscles Early contractures Rigid spine Findings on investigations: Cardiac conduction block Muscle biopsy: Dystrophic changes similar to Duchenne muscular dystrophy Immunohistochemistry: absent Emerin is diagnostic. Investigations to consider: Monitor cardiac function: conduction abnormalities Treatment: Consider insertion of pacemaker Physical … Continue reading Emery-Dreifuss Muscular Dystrophy →

Becker Muscular Dystrophy, BMD

Diagnosis: Must confirm with Western Blotting and genetic testing Quantitative dystrophin analysis by Western blotting: decreased dystrophin Muscle biopsy: Similar findings to Duchenne muscular dystrophy, but less severe. Immunohistochemistry: variation in staining for dystrophin between and within fibres. Use antibodies against different regions of dystrophin to avoid false negatives. Must confirm with Western Blotting and … Continue reading Becker Muscular Dystrophy, BMD →

Glycogenoses (glycogen storage diseases)

Pompe disease: Synonyms: a.k.a. type 2 glycogenosis a.k.a. glycogen storage disease type II GSD II a.k.a. acid maltase deficiency, rare: Diagnosis: A type of lysosomal storage disease and a glycogen storage disease. Genetics: GAA gene chr. 17. Protein= alpha glucosidase Autosomal recessive Biochemical assay: Confirms the diagnosis. Enzyme activity: reduced Skin fibroblasts are best Muscle … Continue reading Glycogenoses (glycogen storage diseases) →

Congenital Myopathies

These are the non-dystrophic congenital myopathies Nemaline myopathy a.k.a. nemaline rod myopathy: Clinical features: Floppy infant with facial weakness and respiratory insufficiency. Also see adult from a.k.a. sporadic late onset nemaline myopathy Genetics: Heterogeneous, Autosomal dominant, autosomal recessive Mutations in the following Proteins: Alpha-skeletal actin Nebulin Troponin. Muscle biopsy: HE fibre atrophy without grouping, subsarcolemmal … Continue reading Congenital Myopathies →

Limb Girdle Muscular Dystrophies LGMDs

Synonyms: formerly pelvifemoral type, Laden-Mobius variant and scapulohumeral type Diagnosis: Autosomal: most are recessive. Must confirm with genetic testing especially for sarcoglycan and dysferlin. Muscle biopsy: Similar to Duchenne muscular dystrophy Cytoplasmic changes may occur: split fibres, whorls, moth eaten fibres, lobulated fibres Hints to subtypes: GMT, Rimmed vacuoles= Telethoninopathy LGMD2G GMT, Rod-like structures= myotilinopathy … Continue reading Limb Girdle Muscular Dystrophies LGMDs →

Duchenne Muscular Dystrophy, DMD

Diagnosis: Genetic testing confirms the diagnosis, as does muscle biopsy Muscle biopsy: Early: variation in fibre size, atrophic fibres, round hypertrophied fibres, centronucleation, regenerating fibres, split fibres. Endomysial connective tissue begins to appear. Later: infiltration by adipose tissue. Poor differentiation of fibre type on ATPase reactions. Inflammatory infiltrates may occur. Immunohistochemistry: total absence of dystrophin … Continue reading Duchenne Muscular Dystrophy, DMD →

Malignant Hyperthermia Syndrome

Genetics: Autosomal dominant Ca++ ryanodine receptor 1 RYR1. Ca++ CACN1A3 muscle DPH sensitive Ca++ channel Clinical features: Hyperthermia Rigidity, tachycardia, hypertension, fever, rising CO2, lactic acidosis, rhabdomyolysis Triggered by anesthetic administration e.g. halothane. Also suxamethonium Findings on investigations: Rhabdomyolysis Muscle biopsy: Normal or Non-specific changes Or pre-existing underlying myopathy: central core disease. Some forms of … Continue reading Malignant Hyperthermia Syndrome →

Hyperkalemic Periodic Paralysis

Synonyms: formerly Gamstorps disease, adynamia episodica hereditaria Genetics: SCN4A 17q23, M1592V. Cold induced weakness I693T Autosomal dominant Mutations in sodium channel alfa subunit SCN4A Clinical features: Recurrent attacks of weakness. All limbs, spares, respiratory and ocular Weakness after exercise. Myotonia may occur e.g. cold induced Precipitated by K+. Alleviated by Ca++. Improves with age Findings … Continue reading Hyperkalemic Periodic Paralysis →

Hypokalemic Periodic Paralysis

Genetics: Autosomal dominant, reduced penetrance in females Ca++ CACN1A3 muscle DPH sensitive Ca++ channel. CACNL1A3 (CACNA1S) gene chr. 1q32 protein= calcium channel L type 1S subunit, Na+ SCNA4A 17q23-q25.3. Or sodium channel alfa subunit SCN4A gene chr. 17q25 Or potassium channel KCNE3 gene chr. 11q13 Clinical features: Commonest form. Recurrent attacks of flaccid weakness. Attacks … Continue reading Hypokalemic Periodic Paralysis →

Dyskalemic Myopathy

Diagnosis: Hyper- or Hypo-kalemia causing a myopathy Findings on investigations: +CK markedly raised Muscle Biopsy: swelling, vacuolation. If severe, necrosis. Related articles: Myopathy, Hypokalemic periodic paralysis, hyperkalemic periodic paralysis,

Statin Myopathy

Diagnosis: Clinical features consistent with statin myopathy, exclusion of other causes and improvement of myopathy on discontinuation of statin. Antibody tests can be useful in distinguishig between statin induced necrotizing myopathy and necrotizing autoimmune myopathy. Clinical features: Proximal symmetric muscle weakness, usually spares the face, bulbar muscles and sphincters CK: usually elevated, may be normal … Continue reading Statin Myopathy →

Drug Induced Myopathies

Corticosteroid myopathy: See under corticosteroid myopathy Statin myopathy: See under statin myopathy Ziduvodine Mitochondrial myopathy: +Muscle biopsy: Ragged red fibres. COX negative fibres, Pleomorphic mitochondria Distinguishes it from HIV associated inflammatory myopathy Choroquine neuromyopathy +Muscle biopsy: Vacuolar myopathy, especially in type 1 fibres. PAS positive. Electron microscopy: muscle and nerve. Membranous whorlings, myelin figures, curvilinear … Continue reading Drug Induced Myopathies →

Critical Care Myopathy

Synonyms: a.k.a. acute quadriplegic myopathy Diagnosis: This is a clinical diagnosis supported by exclusion of other causes. Usually it does not require biopsy but often it is used in cases of uncertainty Clinical features: All limbs, diaphragmatic and intercostal weakness, Occurs in severe illness +/-sepsis, +/-steroids, +/-neuromuscular blocking agents Findings on investigations: +CK normal or … Continue reading Critical Care Myopathy →

Corticosteroid Myopathy

Synonyms: Steroid induce myopathy Diagnosis: This is a clinical diagnosis supported by exclusion of other causes. Usually it does not require biopsy but often it is used in cases of uncertainty Clinical features: Proximal weakness, usually gradual onset Findings on investigations: +/-CK normal or reduced +/-Muscle biopsy: Type 2 fibre atrophy, especially type 2B. Lipid … Continue reading Corticosteroid Myopathy →

Eosinophilic Myositis and Eosinophilic Fasciitis

Eosinophilic myositis Occurs in hypereosinophilic syndrome, parasitic infections, Churg Strauss syndrome, Muscle biopsy: Inflammatory cells including eosinophils   Eosinophilic fasciitis a.k.a. Shulman syndrome: Clinical features: Subcutaneous induration sparing the face and fingers Stiff joints FBC: raised eosinophils Biopsy: Scleroinflammatory lesions in the fascia, may extend into the dermis or muscle. Well circumscribed or absent eosinophilia … Continue reading Eosinophilic Myositis and Eosinophilic Fasciitis →

Macrophagic Myofasciitis MMF

Diagnosis: This is pathological diagnosis Muscle biopsy: Perimuscular infiltrate of large macrophages with PAS positive granular cytoplasm (slightly basophilic on H and E stain). Lymphocytic infiltrate. Usually in deltoid Related articles: Myopathy,

Nodular Focal Myositis

Diagnosis: The diagnosis is confirmed by muscle biopsy Seen in rheumatoid arthritis and other connective tissue diseases Muscle biopsy: Interstitial lymphocyte and plasma cell infiltration forming nodules 1 to 2mm diameter near arteries or arterioles. No invasion of the vessels. Related articles: Myopathy,

Polymyalgia Rheumatica

Diagnosis: Clinical +ESR and CRP: high Note: this is a variant of giant cell arteritis. Weakness does not occur Clinical features: Burning tearing pain around shoulder girdle and arms Investigations to consider: ESR, CRP FBC: anemia in some cases CK: normal EMG: normal Treatment: Prednisolone P.O. low dose Maintenance for 1 year, monitor clinically and … Continue reading Polymyalgia Rheumatica →

Inclusion Body Myositis

Synonyms: a.k.a. inclusion body myopathy IBM Diagnosis: Clinical +Muscle biopsy +neurophysiology Clinical features: Usually >50 year old patients Progressive weakness of quadriceps, ankle dorsiflexors, finger flexors and facial muscles. Dysphagia is common. Pathology, Muscle biopsy Inflammation HE: Rimmed vacuoles: Basophilic granules around vacuoles. Endomysial and perivascular lymphocytes. Increased connective tissue GMT: rimmed vacuoles (red rim), … Continue reading Inclusion Body Myositis →

Parasitic Myositis

Trichinosis, Trichinella spiralis: Diagnosis: Muscle biopsy: encysted larvae. Treatment: Thiabendazole Toxoplasma   Related articles: Myopathy,

Bacterial Myositis

Pyomyositis and Tropical pyomyositis: Features: Very debilitated patients in ICU or tropical form Acute, spontaneous i.e. non-traumatic suppurative infection, abscess formation Gas gangrene, Clostridium perfringens Diagnosis: Traumatic or surgical. Also spontaneous gas gangrene Clostridium septicum in colon cancer patients. Gram stain of bullae fluid: gram positive rods Tissue biopsy may be necesary to confirm the … Continue reading Bacterial Myositis →

Viral Myositis

Acute viral myositis: Viral causes: Influenza virus: Acute benign myositis or rhabdomyolysis. Coxsackie B virus: Bornholm disease or epidemic myalgia AIDS myopathy: HIV associated myopathy: Similar to seronegative polymyositis Muscle biopsy: HIV antigens in the endomysial and perivascular macrophages are usually present Muscle fibres express MHC-1 molecules Primary muscle lymphoma can occur in AIDS patients … Continue reading Viral Myositis →

Myoglobinuria

Diagnosis: Urinalysis for myoglobin Investigations to consider: CK Basic metabolic panel Monitor: K+ and renal function Treatment: Hydration to increase urine volume Treat hyperkalemia Treat the cause Treat renal failure Related articles: Myopathy, rhabdomyolysis,

Rhabdomyolysis

Diagnosis: This is a clinical diagnosis supported by laboratory tests Findings on investigations: +CK markedly raised +/-EMG Florid myopathic motor unit pattern. Spontaneous potentials in many muscles Muscle biopsy, if done: Necrosis of a large number of fibres Other tests: Urinalysis: hematuria on dipstick which is actually myoglobinuria BASIC METABOLIC PANEL: hyperkalemia, hypocalcemia, hyperphosphatemia, hyperuricemia … Continue reading Rhabdomyolysis →

Polymyositis

Clinical features: Proximal muscle weakness; may be asymmetric. Muscle wasting is late Shoulder girdle tenderness (may be absent) Dysphagia & neck muscle weakness may occur Spares face muscles & ocular muscles Muscle biopsy: Endomysial (within the fascicles): muscle fibre necrosis, lymphocytes (absence of eosinophils & plasma cells). Absence of rimmed vacuoles. Surrounding healthy fibres. If … Continue reading Polymyositis →

Dermatomyositis

 Clinical features: Heliotrope ‘lilac/purple blue’ rash around the eyelids, malar region, extensors, knuckles, trunk Gottron’s papules on hand dorsum Nailfold telangiectasia & erythema Nail changes; thickening, cracking Proximal Muscle weakness Findings on investigations: Nerve conduction studies/electromyography NCS/EMG: MUAP Myopathic recruitment On activation: Short duration, low amplitude polyphasic units Spontaneously: increased activity with fibrillations, complex repetitive … Continue reading Dermatomyositis →

Myopathy (Muscle diseases)

Synonyms: Myopathies, Introduction: Please start with the section on neuromuscular disease patterns for an introduction. Once you determined that the patient likely has a myopathy you will need to consider which type of myopathy to narrow down the differential diagnosis. Clinical features of myopathy: Muscle may be normal, wasted or pseudohypertrophied, depending on the disease … Continue reading Myopathy (Muscle diseases) →