Case of proximal weakness in Case of proximal weakness in an elderly manan elderly man

Nadeem Nadeem A.TalpurA.Talpur, MD, MDUniversity of Florida and University of Florida and ShandsShands

Jacksonville, FLJacksonville, FL

INTRODUCTIONINTRODUCTION

65 years old man with past medical history of 65 years old man with past medical history of diabetes type 2 and diabetes type 2 and dyslipidemiadyslipidemiaRecent exacerbation of progressive symptoms of Recent exacerbation of progressive symptoms of proximal weakness in arms and legsproximal weakness in arms and legsThe exact onset of his symptoms was unclearThe exact onset of his symptoms was unclear

Difficulty raising arms above the head Difficulty raising arms above the head and difficulty getting out of the chairand difficulty getting out of the chairParticularly bothered by Particularly bothered by myalgiasmyalgias and and exertionalexertionalmuscle crampsmuscle crampsReview of systems noticeable for muscle atrophy Review of systems noticeable for muscle atrophy No rashes or joint painNo rashes or joint painNo back pain or bladder dysfunctionNo back pain or bladder dysfunctionNo diplopia, ptosis, or bulbar abnormalities

Review of medications revealed:Review of medications revealed:AtorvastatinAtorvastatin for 4 yearsfor 4 yearsWhile on that agent his CK was 4,000 rangeWhile on that agent his CK was 4,000 rangeAgent was stopped and CK reduced, but still Agent was stopped and CK reduced, but still mildly elevated in the range of 300s mildly elevated in the range of 300s No clinical improvement was noted in his No clinical improvement was noted in his symptoms despite discontinuation of symptoms despite discontinuation of atorvastatinatorvastatin

RESULTSRESULTSPertinent elements of his Neurological exam:Pertinent elements of his Neurological exam:–– Strong neck extensors, but neck flexors (4/5)Strong neck extensors, but neck flexors (4/5)–– Atrophy of the proximal muscles of both armsAtrophy of the proximal muscles of both arms

Strength in the arms (B/L):Strength in the arms (B/L):–– Deltoids (3/5), Biceps (4Deltoids (3/5), Biceps (4--/5), Triceps (4/5), ECR and /5), Triceps (4/5), ECR and

FCR (5/5), APB (5/5), and Ulnar FCR (5/5), APB (5/5), and Ulnar intrinsicsintrinsics (5/5) (5/5) Strength in the legs (B/L):Strength in the legs (B/L):–– IliopsoasIliopsoas, (4+/5), and very minimal weakness of the , (4+/5), and very minimal weakness of the

Gluteus Gluteus maximusmaximus bilaterally (5bilaterally (5--/5). Remaining legs /5). Remaining legs muscles were strongmuscles were strong

Deep tendon reflexes, sensation and cranial nerve Deep tendon reflexes, sensation and cranial nerve examination otherwise normalexamination otherwise normal

Initial Neuromuscular ImpressionsInitial Neuromuscular Impressions

Possible cholesterolPossible cholesterol--lowering agent myopathylowering agent myopathyPossible inflammatory myopathyPossible inflammatory myopathyPossible metabolic myopathyPossible metabolic myopathy

Follow up planFollow up plan–– Electrophysiological studies Electrophysiological studies –– Muscle biopsyMuscle biopsy

Electrophysiological ImpressionElectrophysiological Impression

Study was interpreted as showing:Study was interpreted as showing:Evidence of clear Evidence of clear myopathicmyopathic motor units and motor units and spontaneous activity in proximal arm and leg spontaneous activity in proximal arm and leg musclesmusclesEvidence of probable generalized peripheral Evidence of probable generalized peripheral neuropathy affecting motor and sensory axons neuropathy affecting motor and sensory axons

Differential Diagnosis Differential Diagnosis

Inflammatory myopathiesInflammatory myopathies–– PolymyositPolymyositiiss–– Inclusion body Inclusion body myositismyositis

Metabolic myopathiesMetabolic myopathiesMuscular dystrophies Muscular dystrophies Neuromuscular junction disorder Neuromuscular junction disorder

MUSCLE BIOPSYMUSCLE BIOPSY

Muscle Biopsy ResultsMuscle Biopsy Results

Histopathology of muscle biopsy was interpreted as Histopathology of muscle biopsy was interpreted as showing:showing:Moderately severe muscle atrophy with mixed Moderately severe muscle atrophy with mixed myopathicmyopathic and and neurogenicneurogenic changeschangesMyophosphorylaseMyophosphorylase activity was not detected by activity was not detected by immunohistochemicalimmunohistochemical stainsstainsNo evidence of inflammation or No evidence of inflammation or vasculitisvasculitis

DiscussionDiscussion

McArdleMcArdle’’s Diseases Disease::BackgroundBackground–– In 1951, In 1951, McArdleMcArdle described 1st case in 30 yeardescribed 1st case in 30 year--

old man who experienced pain, weakness and old man who experienced pain, weakness and stiffness after exercise stiffness after exercise

–– In 1959, In 1959, myophosphorylasemyophosphorylase was discovered was discovered and was found to be absent in individuals with and was found to be absent in individuals with McArdleMcArdle’’s diseases disease

GeneticsGenetics

Autosomal recessive disorder Autosomal recessive disorder Rare cases of Rare cases of autosomalautosomal dominant inheritancedominant inheritanceSporadic nonSporadic non--familial cases have been reportedfamilial cases have been reportedMutations of the Mutations of the PYGMPYGM gene located on gene located on chromosomes 11q 13, are usually nonsense or chromosomes 11q 13, are usually nonsense or missensemissense

PathophysiologyPathophysiology

MyophosphorylaseMyophosphorylase catalyzes the removal of 1,4catalyzes the removal of 1,4--glucosyl residues from the glycogen molecule, glucosyl residues from the glycogen molecule, liberating glucose 1liberating glucose 1--phosphate phosphate Consequently, the individual is unable to release Consequently, the individual is unable to release glucose from glycogen storage in muscleglucose from glycogen storage in muscleSymptoms in patients are most likely caused by Symptoms in patients are most likely caused by the pattern of fuel utilization of exercising muscle the pattern of fuel utilization of exercising muscle

EpidemiologyEpidemiology

11--2 per 100,000 population 2 per 100,000 population Only a few hundred cases have been reported Only a few hundred cases have been reported Probably underProbably under--diagnosed because of the mild diagnosed because of the mild symptoms in many patientssymptoms in many patientsMale > FemaleMale > FemaleTypically presents in the second to third decade of Typically presents in the second to third decade of life as limited exercise tolerance life as limited exercise tolerance LateLate--onset (>60y) form is very rarely reportedonset (>60y) form is very rarely reported

Clinical PresentationClinical Presentation

McArdleMcArdle’’s diseases disease..–– Exercise intolerance with Exercise intolerance with myalgiasmyalgias–– Early fatigueEarly fatigue–– Muscle stiffnessMuscle stiffness–– CrampingCramping–– Symptoms relieved by restSymptoms relieved by rest–– Second wind phenomenonSecond wind phenomenon

On ExamOn Exam

Classic and lateClassic and late--onset McArdleonset McArdle’’s diseases disease–– Proximal muscle weakness Proximal muscle weakness –– Fixed limb weakness Fixed limb weakness –– Muscle atrophyMuscle atrophy

DiagnosisDiagnosisLabsLabsElevated serum CK levels at rest Elevated serum CK levels at rest No rise of venous lactate after ischemic forearm exercise test uNo rise of venous lactate after ischemic forearm exercise test usually sually seen as (flat venous lactate level)seen as (flat venous lactate level)

ElectrophysiologyElectrophysiologyEMG EMG –– Abnormal spontaneous activity (fibrillation potentials, positivAbnormal spontaneous activity (fibrillation potentials, positive e sharp waves) and sharp waves) and myopathicmyopathic motor unit action potentials motor unit action potentials

GeneticsGeneticsAnalysis of DNA gene test for mutation in leukocytes Analysis of DNA gene test for mutation in leukocytes

BiopsyBiopsySubsarcolemmalSubsarcolemmal vacuoles with deposits of glycogen vacuoles with deposits of glycogen on (PAS) and Masson on (PAS) and Masson trichrometrichrome stainsstainsTotal lack of Total lack of myophosphorylasemyophosphorylase activity activity

ManagementManagement

DIETDIET–– Attempt to bypass the metabolic block by Attempt to bypass the metabolic block by

providing glucose or fructose providing glucose or fructose –– HighHigh--protein diet may beneficial protein diet may beneficial –– Vitamin BVitamin B--66

TAKE ADVANTAGE OF SECOND WINDTAKE ADVANTAGE OF SECOND WINDPHENOMENONPHENOMENON

CONCLUSIONCONCLUSION

McArdleMcArdle’’s diseases disease

Late onset is very rare, only few cases has been Late onset is very rare, only few cases has been reported in literaturereported in literatureClinical picture may be nonspecific and highly Clinical picture may be nonspecific and highly variablevariableElderly patients with proximal myopathy should Elderly patients with proximal myopathy should consider McArdleconsider McArdle’’s disease in the differentials disease in the differentialAs in my case with onset in 7As in my case with onset in 7th th decade decade