[NEURO3] 1.4.04 DISORDERS OF LOWER MOTOR NEURON.pdf

NEUROSCIENCES III DISORDERS OF LOWER MOTOR 08 23 23 NEURON...

NEUROSCIENCES III DISORDERS OF LOWER MOTOR 08 23 23 NEURON LE 1 | MOD 4 | TRANS 04 MAELA P. PALISOC, M.D DPPS, FCNSP, FPNA OUTLINE ☤ Interruption in the motor pathway at a specific level, whether I. Introduction motor pathway from the cortex down to the spinal cord, will II. History Taking determine the type of motor paralysis the patient will present A. Central Hypotonia VS Peripheral Hypotonia III. Neurologic Examination Table 1. Upper Motor Neuron VS Lower Motor Neuron IV. Lower Motor Neuron Weakness V. Acute Flaccid Paralysis UPPER MOTOR NEURON LOWER MOTOR NEURON VI. Anterior Horn Cell Disorder Paralysis affect movement Individual muscle or group of rather than muscle (paresis) muscles are affected A. Poliomyelitis (paralysis) B. Spinal Muscular Atrophy VII. Diseases of Neuromuscular Junction Muscle wasting is only from Wasting pronounced VIII. Diseases of the Muscle (Myopathies) disease, therefore slight. IX. Summary Occasionally mark in chronic severe lesion (disuse) X. Case Synchronous Session XI. Appendix Spasticity/ of clasp knife type Flaccidity Muscle hypertonic Muscle hypotonic/areflexic LEGENDS (+) Clonus (-) Clonus Must know Lecturer Book Presentation OldTrans (+) Babinski (-) Babinski ★ ☤ 🕮 ⎘ ✐ [lec] [bk] [pt] [ot] ☤ the Muscle wasting is not immediately prominent in patients with UMN lesions especially during the very early stage. OBJECTIVES  After completing this lecture, you should be able to: II. HISTORY TAKING  Characterize the distinguishing features of the following: A. UPPER AND LOWER MOTOR NEURON  Upper motor neuron vs. Lower motor neuron  Signs and symptoms of central vs. peripheral Table 2. Difference between Central and Peripheral hypotonia hypotonia  Distinguishing features of muscle tone vs. muscle CENTRAL HYPOTONIA PERIPHERAL HYPOTONIA weakness (UMN) (LMN)  Create differential diagnosis for neuromuscular disorder. Depressed LOC Alert look  Discuss the appropriate medical and diagnostic evaluation of diseases of neuromuscular disorder. Seizure Weak cry and suck (fatigable High-ptched/unusual cry cry) I. INTRODUCTION Hyperactive DTR Areflexia/ hypo Hypotonia Fasciculation Developmental delay Weakness with paucity of spontaneous movement Dysmorphic features, Myopathic facies microcephaly, MCA ☤ Characterized as tented or ☤ Meaning, pictures of inverted V-shaped lip, long malformation or defect face, and high arch palate 60-80% of cases 15-30% of cases DDx: DDx:  Cerebral Palsy  Congenital myopathy  Hypoxic  Congenital myotonic Figure 1. The Anatomy of Lower and Upper Motor Neuron  Ischemic dystrophy Encephalopathy  SMA ☤ the pathway affected in a patient with paralysis is the corticospinal tract or the descending pathway. Lesions involving Normal Creatinine Kinase Raised (or normal) the corticospinal tract are responsible for “Upper Motor Neuron Creatinine Kinase Paralysis”. The corticospinal tract ends in the anterior horn cell of Apnea, irregular respiration Prolonged breathing the spinal cord. difficulties, ventilator ☤ This neuron plus the motor roots and the peripheral nerve will dependence innervate the neuromuscular junction and transmit signal to the Multiple congenital History of polyhydramnios skeletal muscles and this consists of lower motor neurons. abnormalities [NEURO3] Araos, Borromeo, Gonzales, Ong, Portic TH Paulino 1 of 20 1.4.04 DISORDERS OF THE LOWER MOTOR NEURON ☤ Central hypotonia involves the brain,  Cerebral Palsy  Descended arms and ☤ Peripheral hypotonia involves the anterior horn cell to the  Semi-flexed arms, elbows, elbows hips and knees  Jug handle hands (internal muscle.  ☤ Lying supine with legs flexed rotation) ☤ History of fetal movement in utero, fetal presentation, increased and arms adducted  On supine, one can amount of amniotic fluid (particularly Polyhydramnios), low appreciate “frog-like APGAR score, and neurologic examination are important posture” differentiating factors and phenotypic character.  Reduced spontaneous movement ☤ Both central and peripheral hypotonia have problems in  Legs fully abducted and respiration but the pathology in peripheral is due to weakness of arms lying beside the the intercostal muscle and the diaphragm. body, either extended or flexed  ☤ Inability to maintain PERIPHERAL HYPOTONIA normal posture against  Floppy Infant gravity, diminished  “frog-like posture”; “Rag doll” resistance to passive  Inability to maintain normal posture against gravity movements, and excessive  Diminished resistance to passive movements range of joint mobility.  Excessive range of joint mobility HORIZONTAL SUSPENSION  Principal presenting feature of most NMDs in newborn is  Head is lifted when infant is  Rag doll appearance hypotonia or floppy infant already 2  Inverted U-shape  The head should rise and the  Weakness B. MUSCLE TONE AND MUSCLE STRENGHT hips should flex  Very poor muscle tone on  ☤ The infant is suspended in his Paraspinus prone position with the  Rag doll on ventral or examiner’s hand underneath horizontal suspension the chest  Drape over the physician’s hands forming a U-shape  ☤ In hypotonic infants, there will be head lag and legs appear to be limping, forming an inverted U Figure 2. Muscle tone VS Muscle strength posture ☤ The decrease or absence in muscle tone is NOT synonymous with weakness. You can be weak but have normal or increased muscle tone. ☤ Muscle tone is the resistance of muscle to stretch. Therefore, hypotonia is diminished resistance of muscle to passive stretching while weakness is diminished muscle for power or strength. VERTICAL SUSPENSION/ SHOULDER SLIP III. NEUROLOGIC EXAM THROUGH MANEUVER C. NORMAL VS HYPOTONIC INFANT Table 3. Normal VS Hypotonic Infant NORMAL HYPOTONIC RESTING POSITION  Adducts arms when lifted up  Wing their arms due to low on the armpit tone and slips through the  Legs are flexed and hands adducted  Legs and hips are  ☤ Arms are adducted, legs extended are flexed, upright position of  ☤ Elevation of the shoulder the head and shoulders. and arms and extension of the legs [NEURO3] Araos, Borromeo, Gonzales, Ong, Portic TH Paulino 2 of 20 1.4.04 DISORDERS OF THE LOWER MOTOR NEURON TRACTION RESPONE/ PULL-TO-SIT Figure 4. High – arched palate in myopathic facies  Few seconds of head flexion  Marked head lag on pull to  The lift of the head is almost sit maneuver parallel to the body. There is  Infant’s head slightly flexion in all limb joint behind the body and then falls forward upon reaching the sitting position  Excessive head lag, hyperextension, or absence of flexion of the Figure 5. Inverted V shaped lips and High – arched palate in myopathic facies arms and legs are evident when the infant is pulled by the arms from a supine to sitting position, demonstrating an abnormal traction response. D. NON-NEUROLOGIC MANIFESTATION OF PERIPHERAL HYPOTONIA Figure 6. Hyperlaxity of the hand, wrist, and finger joints – 1st symptom of Ocular MG Figure 7. The W-position is a physical finding indicative of joint hyperlaxity that accompanies hypotonia. Figure 3. Facial weakness with myopathic facies ☤ Characterized as invertedly shaped lips and eyelid lag Figure 8. Ptosis and external ophthalmoplegia in a floppy weak child can be seen in a patient with myasthenia gravis. [NEURO3] Araos, Borromeo, Gonzales, Ong, Portic TH Paulino 3 of 20 1.4.04 DISORDERS OF THE LOWER MOTOR NEURON Figure 9. Pectus excavatum in congenital myopathy and Pectus carinatum in spinal muscular atrophy Figure 13. Bilateral suprascrotal undescended testes in Congenital Myopathy Figure 10. Persistent Toe walking in Duchenne Muscular Dystrophy Figure 14. Arthrogryposis (fused joints) in decreased fetal movement in utero Spinal Muscular Atrophy Type 0 Figure 11. Muscle cramps in Charcot-Marie-Tooth Disease Figure 15. Cardiomegaly in Pompe Disease Figure 12. Neuromuscular Scoliosis in Duchenne Muscular Dystrophy and Congenital Myopathy Figure 16. Tongue fasciculation [NEURO3] Araos, Borromeo, Gonzales, Ong, Portic TH Paulino 4 of 20 1.4.04 DISORDERS OF THE LOWER MOTOR NEURON A. DIFFERENTIAL LOCALIZATION OF DISEASES PRODUCING HYPOTONIA Figure 17. Muscle fasciculation Figure 21. Differential Localization of Diseases producing Hypotonia (see appendix for larger image) ☤ We must clearly define distribution and pattern of weakness then look at the DTR. If weakness is quite marked or generalized and associated with absence of reflexes, think of ANTERIOR HORN CELL pathology, which we will confirm with fasciculations and neurogenic EMG. Figure 18. Percussion myotonia in Myotonic Dystrophy ☤ To distinguish a PERIPHERAL NERVE from a MUSCLE lesion, it is very important to determine the pattern of weakness, whether ☤ Myotonia is very slow relaxation of muscle after contraction, it is predominantly proximal or distal. regardless of whether it was voluntary or induced by stretch ☤ As a rule in Myopathies (muscle), it is proximal weakness in reflex or electric stimulation. contrast to distal weakness in Neuropathy (peripheral nerve). Except Myotonic Dystrophy, wherein there is DISTAL weakness  Myopathies: PROXIMAL weakness  Neuropathies: DISTAL weakness ☤ Additionally, a lesion in the NMJ has a prominent fluctuating weakness/facial weakness particularly ptosis which may be the only manifestation of Myasthenia Gravis in children. ✐ [Batch ‘24] CK is markedly elevated for Viral Myositis, Pompe Disease, and Duchenne Muscular Dystrophy. It is normal or slightly elevated in HPP and Myotonic Dystrophy, but we don’t usually test it in HPP. V. ACUTE FLACCID PARALYSIS (AFP) A. DOH DEFINITION Figure 19. Tongue myotonia  A clinical syndrome consisting of rapid onset (acute) weakness that in some cases may involve the respiratory IV. LOWER MOTOR NEURON WEAKNESS and bulbar muscles  Causes are varied, ranging from infection to trauma vascular lesions, tumor, GBS, demyelinating disorder, HPP, etc.  ☤ What is the importance of the program of DOH? This is to identify and monitor AFP cases due to poliomyelitis so that appropriate and timely public health measures can be taken to meet the WHO AFP surveillance performance indicator target for polio-free countries. B. CASE DEFINITION  ☤ Acute Flaccid Paralysis. Acute meaning there is sudden onset of paralysis usually the interval from the onset takes place around 3 to 4 days but may extend to 2 weeks. Flaccid meaning there is loss of muscle tone of the affected limbs or part of the body giving a floppy appearance. Paralysis is a Figure 20. Lower motor neuron Disorders. reduction or loss of ability to move the affected limb/s.  A child distal other features  Reduced intrauterine movements  ☤ Tongue fasciculations  Arthrogryposis  ☤ Selective involvement of the axial and intercostal muscle  Respiratory distress but sparing the diaphragm  Feeding problems  ☤ Have alert and bright expression with preserved cognitive  Cranial nerve involvement function  Facial diplegia  ☤ There is no involvement of the facial and EOMs at  Autonomic dysfunction presentation  Cardiac abnormalities, thin ribs, fractures SMA II Type 1  Intermediate form other names Prenatal, congenital SMA,  Sitters: slowly progressive Werdnig-Hoffman disease  ☤ Able to suck and swallow age at onset Prenatal  ☤ Respiration is adequate in early infancy development life expectancy ★ 18 mos Type 3A (prior to 3 years) Type 3B (after 3 years) life expectancy with a natural Almost normal course of disease highest motor milestone Stands and walks achieved other features  May have hand tremor  Resembles muscular dystrophy Type 4 other names Adult SMA age at onset >21 years Figure 23. Myasthenia Gravis life expectancy with a natural Normal course of disease ☤ At myasthenic junction, the decrease in number of ACH-R highest motor milestone Normal resultsin endplate potential of diminished amplitude which fails to achieved trigger action potential. When the transmission fails at many junctions, the power of the whole muscle is reduced which is clinically manifested as weakness SMA DIAGNOSIS AND TREATMENT.  CK is normal  Weakness and fatigability of ocular, bulbar, and extremity  ☤ ECG: tremors as an artifact presenting muscle fibrillation striated muscle  EMG: fasciculation and fibrillation  Age of onset: 11 months to 17 years’ old  Muscle biopsy: denervation pattern  ✐ Pubertal status may affect the clinical manifestation  ☤ pathologic hallmark: progressive denervation pattern  ✐ Higher incidence of ocular MG in prepubertal in muscle biopsy patient  Genetic marker: SMN1 gene deletion (definitive test)  ✐ Generalized MG – post pubertal  ☤ simplest and most definitive for patients with clinical  Juvenile MG: asymmetric ptosis and diplopia - earliest and suspicion and this is the current gold standard. The constant sign absence of SMN1 confirms the diagnosis of SMA.  ☤ autoimmune MG can be unilateral or bilateral but usually  NO CURE for SMA asymmetric ptosis and diplopia are earliest and most  ✐ Currently there is no cure for SMA, however despite constant signs the presence of homozygous division of SMN1 in  Symptomatic late in the day or when tired majority of patients with SMA, researchers are exploring  Trigger: heat, stress, illness, and with exertion and as day several other approaches to treatment and one of this is progresses the antisense oligonucleotide – NUSINERSEN (first  EOM weakness (diplopia); pupillary response is preserved FDA approved treatment for SMA)  Cannot sustain upward gaze for 30-90 sec. – progressive ptosis VII. DISEASE OF THE NEUROMUSCULAR  Repetitive close and open of the fist for 1-2 mins (fatigue of hand muscles and fatigue of deltoid muscles) JUNCTION  ☤ induces rapid fatigue of the hands and cannot elevate the A. BOTULISM hand for more than 1-2 mins  ★ Descending paralysis  ★ Ocular Manifestation: may be 1st and only manifestation  Intake of corn syrup and honey contaminated with C.  Bulbar manifestation: dysarthria, dysphagia, dysphonia, and Botulinum. dyspnea  EMG: Incremental response. No specific antidote  Masticatory weakness: jaw fatigue and closure weakness [NEURO3] Araos, Borromeo, Gonzales, Ong, Portic TH Paulino 8 of 20 1.4.04 DISORDERS OF THE LOWER MOTOR NEURON MYASTHENIC CRISIS VS CHOLINERGIC CRISIS  Thymectomy with high titer Anti-Ach-R Ab and symptomatic for < 2yrs  ☤ What is the difference between your Myasthenic Crisis and  📣 Thymectomy should be considered and might provide Cholinergic Crisis? They have the same symptoms in your a cure. It is most effective for patients who have high titer exam but DIFFERENT HISTORY. of Anti-Ach-R Ab in the plasma and who have been symptomatic for less than 2 years. Thymectomy is Table 5. MYASTHENIC CRISIS VS CHOLINERGIC CRISIS INEFFECTIVE for congenital and familial forms of MG. MYASTHENIC CRISIS CHOLINERGIC CRISIS  TPE if no respond to steroids, provides temporary remission Precipitating factors: Secondary to overdose of  📣 Plasmapheresis is effective in those who do not infection, surgery, stress anticholinesterase respond to steroid but only provides temporary remission. medication  TPE and IVIg: effective if with high circulating level of Anti- Acute/subacute SEVERE Signs & Symptoms: Ach-R Ab INCREASE IN WEAKNESS  INCREASE  reserve for refractory patient with MG crisis WEAKNESS  use to maximize function before thymectomy  abdominal cramps  diarrhea VIII. DISEASE OF THE MUSCLE  profuse sweating  salivation A. CLASSIFICATION OF MYOPATHIES  bradycardia  miosis Table 6. Classification of Myopathies Treatment: Treatment: HEREDITARY ACQUIRED  IV cholinesterase  Supportive 1. Congenital Myopathies 1. Inflammatory Myopathies inhibitors  withholding 2. Muscular Dystrophies 2. Infectious Myopathies  IVIg cholinergic drugs 3. Myotonia and 3. Endocrine Myopathies Channelopathies 4. Thyroid Myopathies  TPE  ☤ Symptoms passes  Gavage feeding 4. Primary Metabolic within a few hours. The  ventilator support Myopathies dose to be restarted 5. Mitochondria must be reconsidered Myopathies unless the patient had taken an overdose that was not prescribed. HEREDITARY MYOPATHIES Table 7. Hereditary Myopathies CONGENITAL MUSCULAR DYSTROPHY MG DIAGNOSIS 1. Nemaline 1. DMD (Duchenne MD),  Blood exam: Anti-Ach-R Ab / Musk Ab, ANA Ab, CK is normal 2. Central Core BMD (Becker MD)  Chest Xray: (enlarged thymus), MRI anterior mediastinum 3. Myotubular 2. Limb-Girdle MD  EMG: more specifically diagnostic than muscle or nerve 4. Congenital Fiber Type 3. Fascioscapulohumeral biopsy Disproportionate MD  RNS result: (+) decremental amplitude of 10% between the 4. Congenital MD 1st and 4th potential **ASSOCIATED WITH (Fukuyama, Muscle, Eye,  Muscle biopsy: role is limited RYR1 RECEPTOR FOR Brain Disease, Walker  ☤ MG is one of the few neuromuscular diseases where EMG MALIGNANT Walburg Syndrome) is more specifically diagnostic than muscle or nerve biopsy. HYPERTHERMIA The neve is electrically stimulated 5 to 6 times and response are obtained. This is called the repetitive nerve stimulation Table 8. Hereditary Myopathies (RNS). If performed in the adductor pollicis stimulating the MYOTONIA AND PRIMARY METABOLIC median nerve for generalized MG and for RNS performed on CHANNELOPATHIES MYOPATHIES orbicularis oculi stimulating the facial nerve. The positive RNS 1. Myotonic Dystrophy 1. Disorder of Glycogen result is decremental amplitude of 10% between the 1st and (DM1)  Pompe Disease 5th compound muscle action potential (CMAP). 2. Periodic Paralysis 2. Disorder of Lipids  ☤ Muscle biopsy the role is limited for MG. You can also  Hypokalemic Metabolism request for Anti-Acetylcholine Receptor Antibody (Anti-Ach-R Periodic Paralysis 3. Mitochondrial Ab)  Hyperkalemic Metabolism Periodic Paralysis 4. Mitochondrial Encephalomyopathies MG TREATMENT  Some patients with mild MG require no treatment.  Cholinesterase inhibitor: Primary therapeutic agent ACQUIRED MYOPATHIES  Pyridostigmine oral tablet (Mestinon) recommended Table 9. Acquired Myopathies initially INFLAMMATORY INFECTIOUS  Dose: 0.5 to 1 mkdose q4-6 Hr (max: 60mkdose) 1. Viral Myositides 1. Juvenile  Max daily recommended dose 7mkday (Influenza) Dermatomyositis  Corticosteroids (Prednisone): autoimmune basis of the 2. Polymyositis 2. Parasitic Myositis disease 3. Immune Mediated 3. Bacterial Myositis  📣 Because of the autoimmune basis of the disease long Necrotizing 4. Fungal Myositis term steroid treatment with prednisone aside from the Myopathy cholinesterase inhibitor. 4. Inclusion Myositis [NEURO3] Araos, Borromeo, Gonzales, Ong, Portic TH Paulino 9 of 20 1.4.04 DISORDERS OF THE LOWER MOTOR NEURON B. MUSCULAR DYSTROPHY (MD) ☤ At birth, the child with DMD are asymptomatic and appears  MD is a group of inherited disease in which the voluntary normal but histological evidence of myopathy and elevated CK muscles progressively weakens overtime. are present already. Short stature may be seen in the pre-  Dystrophy: Abnormal growth symptomatic phase. On the first year of life, affected boys  ★ MD is distinguished from all other neuromuscular disease exhibit mild gross motor delay like delay in seating, standing, by 4 obligatory criteria: and walking. They walk at a mean age of 18 months. Weakness  It is a primary myopathy is noted between 2 and 3 years old, affects proximal before the  It has a genetic basis distal and lower before the upper limbs.  The course is progressive ☤ Between 3 and 6 years old, the so-called honeymoon period  Degenerative and death of muscle fibers occurs at some is noted due to transient improvement in motor milestones but stage in the disease in this period, you can see that they have broad-based gait, exaggerated lordosis, and pseudohypertrophy of the calves. DUCHENNE MUSCULAR DYSTROPHY Due to weak pelvic and girdle muscles, a compensatory mechanism to rise from a lying position is utilized called Gower’s  Most common and severe childhood muscle condition maneuver.  X-linked disorder (1/3 De Novo)  Absence of Dystrophin protein ☤ Between 6 and 10 years old, majority of the affected children develop contracture causing toe walking and limitation of hip  ☤ A negative family history does not exclude the flexion due to progressive weakness. They are wheelchair- diagnosis as de novo mutation occur in 1/3 of cases or bound by the age early teens and 33% develop 30% of cases. cardiomyopathy by 14 years old.  ☤ The dystrophin plays an essential role in the maintenance of membrane integrity during muscle fiber contraction. The absence of dystrophin muscle cells are susceptible to stretch-induced damage and resulting into progressive muscle degeneration and replacement with fat and connective tissue.  Important stabilizer during muscle contraction  Stretch  Induced damage  Degeneration  Fat and Connective Tissue  Found in skeletal muscle, cardiac, and brain DMD and cognitive impairment  DP 140 and DP 71 are predominant in the brain  ☤ Patients with DMD have cognitive impairment because dystrophin isoforms DP 140 and DP 71 are predominant in the brain.  Mutation  Disruption  Increase cognitive impairment  Figure 25. Natural Course of DMD in 5 stages Lower IQ scores in DMD patient  ☤ Mutation causing disrupting brain isoforms DP 140 and DP ☤ Although the age of onset and duration of each stage can vary 71 results in an increased cognitive impairment that leads to from patient to patient and may be affected by pharmacological lower IQ in patients with DMD that’s why patients with DMD and non-pharmacological interventions, each boy with DMD have cognitive impairment or learning disabilities. passes through each of these stages sequentially. Duchenne’s impact on the body DMD laboratory features  Dystrophin abnormalities: learning and cognitive  ☤ How to diagnose patients with DMD? Of course, history, impairment physical examination and neuro examination. You can  Cardiomyopathy  decreased heart function and leads to request for laboratory features which is present in DMD. heart failure  Creatine Kinase: Elevated  Weakens diaphragm  required ventilator  pneumonia  Initial diagnostic test performed when suspecting  Loss of muscle mass  weakness  inflammation and dystrophinopathies fibrosis  Consistently elevated even in pre-symptomatic phase  Brittle and weak  contracture and scoliosis (birth)  50 to 100x elevated  Genetic testing  Dystrophin gene (PCR – 30%)  Muscle Biopsy  Dystrophin Immunohistochemical Staining  More specific  ☤ If the PCR in genetic testing is negative because PCR is usually positive for only 30%. Figure 24. DMD Temporal Profile [NEURO3] Araos, Borromeo, Gonzales, Ong, Portic TH Paulino 10 of 20 1.4.04 DISORDERS OF THE LOWER MOTOR NEURON MANAGEMENT OF DMD Figure 27. Myotonic dystrophy (DM1) ☤ 100% of patients with DM1 presents with myotonia. The muscle weakness in DM1 is mild, slow, and progressive. Patient may appear normal at birth or symptomatic Figure 26. Management of DMD at any age. ☤ The management of DMD is multidisciplinary. We need ☤ You can see myopathic facies, characterized by facial wasting gastroenterologist, pulmonary specialists, cardiologists, and hypotonia (upper left). There is inverted V-shape upper lip medicine, ortho, psychiatrist, and neurologist to manage this (lower left), high arch palate, weak temporal and pterygoid patient. muscles with impaired facial expression. Difficulty in speech and swallowing are common. We have narrow head, elongated face, ☤ The mainstay in the medical treatment of DMD is and characteristic frontal baldness. Typical progressive, distal corticosteroid. It results in preservation of ambulation by up to 1 muscle wasting is the features. One of the features of myotonic to 3 years. The precise mechanism of their effects is unknown. dystrophy compared to other myopathies. Starting therapy between 2 and 5 years of age when strength will ☤ ★ As I said before, as a rule, in myopathy or muscle decline. disorder, weakness is usually proximal except for myotonic dystrophy, which is distal weakness. BECKER MUSCULAR DYSTROPHY ☤ Since this is a multisystemic dysfunction, we start from head to  ☤ Mild form of DMD toe. 50% of patients will have intellectual impairment, 85% will  Abnormal dystrophin have ocular finding of cataract, 76 will have cardiac involvement,  Muscle weakness at 10 years old particularly arrythmias rather than cardiomyopathy which is  ☤ Typically the weakness is on the limb-girdle pattern common in other myopathies. Smooth muscles of the but many without muscle weakness only myalgia gastrointestinal tract are affected and manifested as constipation, with exertion and calf hypertrophy. delayed gastric emptying time, and poor peristalsis.  Ambulate beyond 13 years old ☤ They have multiple endocrine problems, common are diabetes  Only myalgia with exertion and calf hypertrophy mellitus and hypothyroidism. They can have testicular atrophy  Normal IQ and testosterone deficiency are common. They have low level of  Affects the muscles of the hips, pelvic area, thighs, and immunoglobulin G. shoulder as well as heart  A muscle disease with systemic effects C. MYOTONIA AND CHANNELOPATHIES  Myotonia MYOTONIC DSYTROPHY (DM1)  Skeletal muscle wasting  Weakness and wasting of voluntary muscles in the face,  Myotonia (impaired relaxation) neck, and lower arms and legs  Steiner Disease  Muscles between the ribs and those of the diaphragm  Dystrophia myotonia can be weakened.  2nd most common muscular dystrophy  Cardiac arrhythmias  Autosomal dominant disorder (50% chance of inheriting the  The heart is also affected. disease)  Smooth muscle dysfunction  Caused by mutation in DMPK gene (DM protein kinase)  The digestive tract and uterus are often affected.  Cause multiple organ system dysfunction: striated and  Radial cataracts smooth muscles  Cognitive dysfunction  Abnormalities in the brain can lead to excessive sleepiness or apathy  ☤ The DISTAL distribution of muscle wasting in myotonic dystrophy is an EXCEPTION to the general rule of myopathies having proximal and neuropathies having distal distribution patterns. [NEURO3] Araos, Borromeo, Gonzales, Ong, Portic TH Paulino 11 of 20 1.4.04 DISORDERS OF THE LOWER MOTOR NEURON Diagnosis D. ACQUIRED – INFECTIOUS MYOSITIS  ☤ How are you going to diagnose DM1? By physical VIRAL MYOSITIS examination and neurologic exam.  ★ Influenza (☤ A, B, and rarely C): common cause of  History & PE, CK is normal infectious inflammatory myopathy  ☤ if you’re thinking of a muscular disorder, CK is the 1st  ☤ Caused by Upper respiratory tract pathogen laboratory exam that you should request.  Acute infection  CK or creatine kinase in DM1 is normal.  Myalgia (systemic release of cytokines)  EMG: myotonic discharges (high frequency train of action  Fever potential evoked by needle insertion)  Constitutional signs and symptoms  Genetic/DNA test: CTG repeat in DMPK gene (gold  Severe pain, swelling, and muscle tenderness 🡪 after URT standard) subside  Muscle biopsy: NOT necessary (non-specific)  ☤ The pain can be so severe as to interfere with the child’s ability to walk or perform routine activities. Muscle Treatment swelling and induration may be present.  ★ No specific treatment for DM  Weakness can be profound: last for 1 week  But cardiac, endocrine, gastrointestinal, and ocular  ☤ The symptoms are self-limited. complication can be treated  Pathogenesis: muscle damage immune mediated  PT, OT, and multidisciplinary care attack of the virus in the muscle muscle injury  “Warm up phenomenon” myotonia may improve with exercise Diagnosis and Treatment  or repeated movement. Myotonia is rarely a bothersome  ★ History & PE, creatine kinase: MARKEDLY ELEVATED symptom. It is a weakness that is disabling.  ☤ if you do EMG which is rarely done for viral myositis,  Drugs that diminished myotonia and improved functions you can see features of active necrotizing myopathy.  Mexiletine, phenytoin, carbamazepine, procainamide,  Muscle biopsy: RARELY INDICATED and quinidine sulfate (s04)  Treatment: self-limiting, symptomatic, and supportive  ☤ with bedrest, hydration, giving acetaminophen or HYPOKALEMIC PERIODIC PARALYSIS nonsteroidal anti-inflammatory drugs.  Autosomal dominant  Episodic, reversible weakness or paralysis associated with E. HEREDITARY – PRIMARY METABOLIC transient alterations in serum potassium levels, usually MYOPATHIES hypokalemia but occasionally hyperkalemia POMPE DISEASE (GLYCOGEN STORAGE  ★ Diurnal attack of weakness: night or early morning, DISEASE II) oliguria/anuria, myalgia, and constipation  Decrease K^+ during attack  Autosomal recessive disorder  Secondary cause of hypokalemia  ★ Acid maltase deficiency  Poor K^+ intake (alcoholics, anorexia nervosa)  There are 2 clinical forms: Infantile and Juvenile.  Excessive K^+ exertion (diarrhea, laxative abuse,  Severe generalized myopathy and cardiomyopathy profuse sweating – athletic training)  ★ Creatine kinase: markedly elevated  Renal loss of K^+ (RTA, osmotic diuresis)  Muscle biopsy: vacuolar myopathy (with abnormal lysosomal  Provocative stimuli: enzymatic activity such as acid and alkaline phosphatases.  High carb meals and rest after exercise  Treatment: Enzyme replacement therapy (ERT)  Cold and emotional stress/excitement  ☤ has improved this outcome Laboratory Findings Infantile Form  serum electrolytes and ECG during attacks of weakness is  Infantile form: fatal before 2 years old essential to diagnosis and treatment  Respiratory weakness  ☤ if you’re going to do ECG, you’re going to see U wave  Cardiac failure changes in patient with HPP.  The clinical manifestations of infantile form of Pompe disease  Respiratory  Progressive respiratory muscle involvement  Frequent respiratory infection  Sleep-disordered breathing  Musculoskeletal  Progressive MUSCLE WEAKNESS  Profound HYPOTONIA and weak  Delayed motor milestone  Cardiovascular.  Massive CARDIOMEGALY Figure 28. ECG depicting U waves in patient with HPP  Progressive cardiomyopathy  Gastrointestinal Treatment  Hepatomegaly  oral 𝐾 +  Macroglossia  ☤ but if the potassium is really low, you can admit the  Feeding difficulties patient and give intravenous potassium, low Na,  Failure to thrive acetazolamide  Poor weight gain [NEURO3] Araos, Borromeo, Gonzales, Ong, Portic TH Paulino 12 of 20 1.4.04 DISORDERS OF THE LOWER MOTOR NEURON Juvenile Form Core Myopathy (Central Core Myopathy and  Exclusively affects the muscle Multicore Disease)  Much milder myopathy  Central Core Myopathy/Disease (CCD)  ☤ compared to infantile form  Caused by RYR1 (Ryanodine receptor) mutation in  No cardiac and hepatic enlargement 90% of cases  Mimic muscular dystrophy  Significant skeletal abnormalities e.g., chest wall  ☤ Pompe disease is one of the differential diagnoses in deformities, scoliosis, joint contracture, hip dysplasia patients with muscular dystrophy because they also  Spare the eye muscles, facial weakness is an inconstant have a markedly elevated CK. finding  Normal early childhood  High index of cardiac abnormalities  ★ Creatine kinase: greatly elevated (similar to DMD)  Susceptible to malignant hyperthermia  ★ Confirmatory test: quantitative assay of acid maltase  ★ CCD who receives general anesthesia should be pre- activity treated with DANTROLENE Sodium before surgery as  Improve outcome with enzyme replacement therapy a precaution to MALIGNANT HYPERTHERMIA  Treatment: NONE F. CONGENITAL – MALIGNANT  Case control series: Use of Salbutamol improves strength and motor function and forced vital HYPERTHERMIA capacity  Genetic disorder of the skeletal muscle  Multicore Disease (MmD)  ★ Gene: (RYR1) Ryanodine receptor  Mutation:  Hypermetabolic crisis (manifestation)  RYR1 (MmD with ophthalmoplegia)  ☤ such as fast rise in body temperature and severe  SEPN1 (MmD without ophthalmoplegia) muscle contraction when a susceptible individual  Benign receives a general anesthesia or halogenated  Non-progressive generalized hypotonia inhalation, anesthetic agent, or succinylcholine.  Shortly after birth  ★ Trigger: halogenated inhalation, anesthetic agent, or  Almost affected children walked at 2 y/o succinylcholine Myotubular Myopathy Table 10. Symptoms and Treatment of a clinical MH episode  Myotubularin (MTM1) MALIGNANT HYPERTHERMIA  Severe neonatal onset  X-linked recessive Early Signs Later Signs  Subtype: Myotubular myopathy  Increasing 𝐸𝑇𝐶𝑂2  Hyperthermia  Dynamin2 (DNM2)  Tachycardia  Muscle rigidity  most common cause of dominant CNM  Tachypnea  Myoglobinuria  Present in infant and late childhood  Mixed acidosis  Cardiac arrest  Treatment: NONE  Masseter spasm/trismus  Several Case Report: Use of Acetylcholine inhibitor (Pyridostigmine) → modest but definitive improvement in clinical symptomatology  Ptosis and EOM weakness, ophthalmoplegia, congenital  ☤ Where can you find malignant hyperthermia? MH is myopathies, facial weakness  Myotubular myopathy associated with 🕮 myopathies with RYR1 abnormalities.  implies a maturational arrest of fetal muscle during the myotubular stage of development at 8-15 weeks AOG G. MYOPATHIES WITH RYR1 ABNORMALITIES CONGENITAL MYOPATHIES Congenital Muscle Fiber-Type Myopathies  Clinically and genetically heterogeneous group of  Diagnosis based on the context of clinical symptoms of neuromuscular diseases myopathy and fiber-type DISPROPORTION on biopsy.  ★ Most common clinical presentation is in the neonatal  Define only by MUSCLE BIOPSY period as the floppy infant.  Facial weakness is an inconstant finding  An important diagnostic consideration in all individuals with  May develop in association with: muscle weakness.  Nemaline rod disease  Most are STATIC / slowly progressive  Krabbe disease  Most are HEREDITARY few are sporadic / de novo  Cerebellar hypoplasia  Most are autosomal recessive EXCEPT X-linked in  Fetal alcohol syndrome centronuclear myopathies  ★ Requires 3 principal obligatory criteria:  MYOTUBULAR myopathy  Disproportion in the ratio of type 1 and 2 myofibers  Definitive diagnosis is by HISTOPATHOLOGIC findings/ via  Type 1 fibers are uniformly small than positive GENETIC testing normal, whereas type 2 fibers are normal or mildly  CPK level typically NORMAL to maximum 2x to 3x elevated hypertrophic to compensate  NO treatment or therapy  No myofiber degeneration or regeneration  Mutations in TPM3, TPM2, RYR1, SEPN1, and ACTA1 [NEURO3] Araos, Borromeo, Gonzales, Ong, Portic TH Paulino 13 of 20 1.4.04 DISORDERS OF THE LOWER MOTOR NEURON Nemaline Myopathy it is a mixed type of hypotonia kasi may central lesion,  Characterized in general by the presence of significant bulbar maliit and ulo or microcephaly. dysfunction (because of lower face and neck flexor  Hypotonia per se is not only for lower motor neuron, it weakness) in the setting of additional and variable extremity can be diagnosed as central hypotonia or mixed type weakness hypotonia, or peripheral hypotonia  congenital myopathy with facial weakness sparing the eye  Hypotonia is caused by disorder that affects any level of the muscles nervous system  Types:  Severe congenital NM STEP 2 KEY ELEMENTS IN THE PATIENT’S  Intermediate congenital NM HISTORY  Typical congenital NM  Childhood / Juvenile-onset NM  Dapat alam na ang mga itatanong sa patient since this will be  Adult-onset NM our job during the clerkship and internship and encode it in  ACTA1 the database  Most common cause of severe congenital NM  Details of the pregnancy, delivery, and postnatal period  Nebulin (NEB)  Hip subluxation / arthrogryposis – likelihood of hypotonia  Most frequently encountered with typical congenital NM in utero  Treatment: NONE  Ask about quickening, or count movement of the  Case series: Use of L-thyroxine improves bulbar baby symptoms and sialorrhea  IEM – normal pregnancy and delivery, hypotonia after  Some cases will have periodic paralysis and King- D1 or D2 of life Denborough syndrome  Post – term and Pre – term deliveries  Periodic Paralysis  Infections such as Toxoplasmosis, TORCH infection  Episodic, reversible weakness or paralysis associated  Alcohol and Drug usage during pre or post – natal insult with transient alterations in serum potassium levels, increase the probability of CNS dysfunction as usually hypokalemia but occasionally hyperkalemia underlying etiology of low tone or hypotonia  Inborn Error of Metabolism should also be suspected in  ★ Familial forms are caused by mutations in genes infant with normal pregnancy and delivery encoding voltage-gated ion channels in muscle: Na,  Day 0 – normal and on Day 1 or 2 – Hypotonic or Ca++, K like rag doll, so one of the differential would be  King-Denborough Syndrome mixed hypotonia or central hypotonia just like in IEM  Developmental assessment IX. SUMMARY  Motor delay with normal social and language  We reviewed the difference between: development decrease likelihood of brain pathology  Upper motor neuron vs lower motor neuron  Probably not CNS but Peripheral only  Signs and symptoms of central vs peripheral hypotonia  Example: associated with LMN and Mental Retardation  Distinguishing features of muscle tone vs muscle in male, hypertrophic calves, pseudo hypertrophy of the weakness calves – DUCHENNE MUSCULAR DYSTROPHY  We talked about the differential diagnosis for lower motor  Not necessarily central but weakness is secondary neuron disease from anterior horn cell, peripheral nerve, NMJ to muscle disorder and muscle.  Dietary / feeding history  We discussed the appropriate medical and diagnostic  Decrease of NM junction sucking / swallowing – fatigue evaluation for lower motor neuron disease. or get worse with repetition  Pag neonate, we test for sucking reflex and rooting X. CASE SYNCHRONOUS SESSION reflex, very important to Lower motor neuron A. OBJECTIVES disease  After completing this lecture, you should be able to answer  Example: Prader willi syndrome the following:  Characteristic of hypotonia, obesity, mental  Where is the lesion? Anatomic localization retardation, and hypogonadism  What is the diagnosis? Etiologic diagnosis  It is characterized by infant feeding difficult and  What are the Diagnostic studies to be requested? failure to thrive pero mataba sila  How are you going to manage the patient?  Infantile botulism – honey syrup or corn syrup consumption contaminated by Clostridum botulinum. B. STEPS  Family history similar illness  Delayed motor milestones (congenital myopathy) STEP 1 – UNDERSTANDING THE TERMINOLOGY  Very revealing  Muscle tone: resistance of muscle to stretch  Repeated abortion – suggest of variety of disorder with  HYPOTONIA is diminished resistance to muscle to passive pre-natal onset or developmental delay stretching  Chromosomal abnormality  WEAKNESS is diminished muscle power or strength  Delayed motor milestone – congenital myopathy  GRADES: 5/5 ,4/5  Premature death - metabolic diseases  While weak infant is always hypotonic, hypotonic is often present with normal strength STEP 3 PHYSICAL EXAMINATION  Deep Tendon Reflex will follow to determine  Degree of hypotonia  Sometimes you will see patients in your practice or clinic  Frog legged that hypotonic talaga sila and yet maliit and ulo. So it doesn’t mean na lower motor neuron lang and problem,  hips adducted, and knee flexed  Lack of spontaneous movement suggest weakness [NEURO3] Araos, Borromeo, Gonzales, Ong, Portic TH Paulino 14 of 20 1.4.04 DISORDERS OF THE LOWER MOTOR NEURON  Initially assessed with the infant’s posture while in  Hepatomegaly – lysosomal and glycogen disease supine STEP 4 INVESTIGATION  Brain neuroimaging  If there is GOOD EVIDENCE FOR CNS DYSFUNCTION  Microcephalic, Macro/megacephalic  Karyotyping  Dysmorphic features  EXAMPLE: Down syndrome  Muscle disorder / NMJ  CPK test is useful (INITIAL SCREENING) Figure 29. Frog - legged  Wanted to know if it muscle or not  Assessing tone – should be alert but not crying  Keep in mind that congenital myopathies are associated  DTR – most valuable aspect of NE with normal CPK  Anterior horn cell – mild increase in CPK  Brisk reflex or clonus – indicated CNS dysfunction  Congenital MUSCULAR dystrophy – CPK Increase  Diminished or absent reflexes – points strongly to Lower significantly motor neuron  10x or 100x increase – Duchenne Muscular  Weak + Clonus = CNS dysfunction than peripheral dystrophy  Extremity tone – assessed by passive movement  Horizontal and Vertical suspension – truncal and nuchal tone Following initial screening and non-invasive  Abilities need to be compared with age – appropriate investigation developmental norms  EMG, NCV, and muscle biopsy  Narrows down differential diagnosis  IF muscle biopsy or EMF is considered BLOOD CPK TEST  Dysmorphic features should be drawn before these procedure (may cause short-  Likelihood of CNS dysfunction as example of hypotonia term elevation of CPK level)  EXAMPLE: Down syndrome  EMG then CPK with increase CPK result, May result to  Hypotonic at birth false positive due to needle damage to the muscle  Dysmorphic features: hypertelorism, Low set of  Advances is genetic testing ears  Muscle biopsies are not performed  Anterior Horn cell spares EOM  Invasive procedure  Gising sila but body is paralyzed  Do sedation and refer to anesthesia  NMJ – ptosis and EOM weakness  Sample: Blood only  Ocular Myasthenia gravis – most common and  Also used in epilepsy and cancer initially as is and spectrum continues to generalized  Many muscular disorder that present with hypotonia in myasthenia gravis newborn can only be diagnosed specifically using muscle  Long narrow face indicate muscle weakness – myotonic biopsy dystrophy  Specific genetic testing  SMA – SMN1 - survival motor neuron 1 gene  DMD – dystrophin protein gene  DM1 – DMPK gene C. CASE CASE 1: Q.C 5 – month – old girl  CC: unable to raise her upper body when lying prone  History  No Attempts to roll over  Rarely moved her legs and made no attempts to push with her feet when held upright  She laughed and interacted with those around her and Figure 30. Long narrow face became excited at the sight of food  She often squealed and seemed to respond to her name  No loss of milestones was reported  Attention of quality of cry  Uneventful: Past Medical, Family History, Birth and  High pitched / unusual sounding – CNS pathology Maternal History  Weak cry – diaphragmatic weakness  With 7-year-old healthy male sibling  Di sya makahinga or makaiyak dahil sa muscles  Physical Examination nya sa diagphram parang naririnig lang siya na  Infant looked well umuungol  No dysmorphic features  Fatigable cry – Congenital MG  Height, weight and head circumference were all within  Head to toe PE normal percentiles  PE is required to assess for potentially associated organ  Cranial nerves were normal including EOM’s dysfunction and to recognize the existing syndrome  Marked hypotonia on horizontal and vertical suspension  Hypotonia + cardiac failure – muscle or mitochondrial  tightness of the hip adductors and knee extensors was disease noted [NEURO3] Araos, Borromeo, Gonzales, Ong, Portic TH Paulino 15 of 20 1.4.04 DISORDERS OF THE LOWER MOTOR NEURON  weak grasp and unable to reach forward  primitive reflexes were absent, DTR’s not elicited Question and Answer  WHAT IS THE LESION?  Lower Motor Neuron  WHAT IS THE PATTERN/DISTRIBUTION?  Generalized  WHERE IS THE LESION?  Anterior Horn cell  Reason: spared EOMs  PERIPHERAL NERVOUS SYSTEM PATHWAY  Anterior Horn Cell – located at the anterior gray matter Peripheral Nerve Neuromuscular Junction (NMJ) Muscle  ETIOLOGY OF THE LESION  Spinal Muscular Atrophy (TYPE 1)  DIAGNOSTICS/ INVESTIGATION  SMN 1 gene: Survival Motor Neuron 1 Gene (last)  Definitive test Figure 32. Marked distal muscle weakness and hypotonia  Creatinine Kinase – 1ST thing to do  Result is Normal  EMG – CV Question and Answer  Result: denervation pattern  WHAT IS THE LESION?  MANAGEMENT  Lower Motor Neuron  No Cure, Symptomatic supportive  PE: distal weakness and hypotonia  In Other Countries, NUSINERSEN, an antisense  WHERE IS THE LESION? oligonucleotide drug for SMA  Muscle  1st FDA approved therapy for SMA  ETIOLOGIC DIAGNOSIS  Antisense oligonucleotide (ASO)  Myotonic Dystrophy (DM1)  MOA: alter splicing of SMN2 pre mRNA and thus  DEFINITIVE DIAGNOSTIC TEST increase the amount of functional SMN protein  CK: Normal  Given intrathecal injection  EMG-NCV: Myotonic discharges  Parang lumbar puncture in between L2 – L3  Muscle biopsy: Nonspecific  1st year 750,000 USD and 375,000 USED every  Genetic Testing: Definitive Diagnosis – DMTK year thereafter  Myotonic Dystroby CTG repeat (positive)  Risdiplam (Evrysdi) – Given orally  TREATMENT OF CHOICE:  No specific medical treatment but since this is multisystemic disease, you only have to manage it CASE 2: JV, 15-year old male symptomatically.  CC: Clumsy and weak during cold temperature and rest  Drugs that diminished myotonia and improved functions:  History Mexiletine, Phenytoin, Carbamazepine, Procainamide,  He is described as clumsy with distal muscle weakness, and Quinidine SO4 – just to alleviate the symptoms of associated with muscle pain, and stiffness aggravated myotonia with cold temperature and rest.  At 4 years old, he had cataract extraction and developed CASE 3: JR, 10-year old boy muscle stiffness and cardiac dysrhythmia after induction of opioid anesthesia. Surgery was then deferred.  CC: waddling gait and pseudohypertrophy  GP diagnosis was global developmental delay (GDD)  He was brought for consult for his funny slow gait. due to motor weakness, language difficulty, speech  History delay, and hearing loss.  He had no issues until 2 years of age when he persisted  PE/NE: with toe walking associated with some difficulty climbing  showed marked facial weakness, cataract, triangular stairs and running. shape mouth, weak grip, percussion of muscle results to  PE/NE very slow relaxation of muscle, marked distal muscle  non-dysmorphic boy with average cognition, proximal weakness, and hypotonia. weakness, hypertrophic calves  CK is normal.  CK: Markedly elevated at 10,000 u/L. Figure 32. Pseudo hypertrophic calves and waddling gait Figure 31. very slow relaxation of the muscle [NEURO3] Araos, Borromeo, Gonzales, Ong, Portic TH Paulino 16 of 20 1.4.04 DISORDERS OF THE LOWER MOTOR NEURON Question and Answer Question and Answer  WHAT IS THE LESION?  WHERE/ WHAT IS THE LESION?  Lower Motor Neuron Lesion  Anatomic localization: Peripheral nervous system: LMN:  WHERE IS THE LESION? NMJ  Muscle  ETIOLOGIC DIAGNOSIS?  The number one hint that explains why this is a  Myasthenia Gravis muscle lesion is the CK.  DIAGNOSTIC EVALUATION?  CK is the product of muscle metabolism. But not all  Anti-acetylcholine receptor antibody normal CK are not muscle kasi Myotonic Dystrophy  EMG-RNS: decremental response has a normal CK.  CK is normal  ETIOLOGY OF THE LESION?  MANAGEMENT  Muscular Dystrophy (DMD, BMD)  Choline esterase inhibitor: Pyridostigmine  Aside from Muscular Dystrophy, you can consider  Steroids Pompe Disease as a differential diagnosis because  IV immunoglobulin of the markedly elevated CK.  Plasmapheresis  Another differential with elevated CK is Viral  Preparation before referral to neuro department Myositis.  Intubate – secure airway  You cannot consider Spinal Muscular Atrophy  Give IVIg because the CK would be normal or increase 5x but  This is not peripheral nerve. In peripheral nerve, there is not reach 10,000 u/l. sensory and motor. This is Myasthenia Gravis, okay sa  Kapag tinusok mo yung muscle and you get the CK, umaga pero pagdating sa hapon pagod na. Since 5 years old, talagang mataas siya kasi you damaged the JUVENILE MG. Kung wala itong proximal muscle weakness, muscle. it is more of Ocular MG.  So do NOT do CK after performing EMG-NCV  Saan mo makikita ang INCREMENTAL RESPONSE?  DMD has early manifestations, while BMD (and Lambert-Eaton and Botulism. Botulism has Pompe) presents later in life and symptoms are not DESCENDING paralysis. Flaccid paralysis is a generic so pronounced. term, can be seen in GBS, tumor, Polio, Hypokalemic  DIAGNOSTIC Periodic Paralysis.  Creatinine Kinase: markedly elevated (50-100x  In short, Botulinum has INCREMENTAL response and increased) DESCENDING paralysis. In NMJ lesion, it has  INITIAL TEST DECREMENTAL response and fluctuating paralysis or  EMG-NCV: short duration, small amplitude, polyphasic weakness. potential  GBS had ASCENDING paralysis. Lesion is localized in the  Genetic testing: dystrophin gene Peripheral Nerve, not NMJ! It affects the sensory as well as  Muscle Biopsy: Dystrophin Immunohistochemical the motor. Pwede siyang asymmetric, at pwede ilagay sa staining (more specific) Acute Flaccid Paralysis. Take note of this.  After CK, your next step is Genetic Testing. If the patient  Pyridostigmine is the DOC for Myasthenia Gravis. is negative for Dystrophin, but you are very sure that this Sometimes when MG is very severe, we use steroids. is Muscular Dystrophy, then you do muscle biopsy with Sometimes when there is Thymoma, we give IVIg and immunohistochemistry stain of dystrophin which is more Plasmapheresis pre-op specific. Kasi not all muscular dystrophy is positive for  Kung sa tingin mo may Thymoma ang patient, you can check dystrophin kasi 30% are negative. with Anti-acetylcholine receptor antibody  MANAGEMENT  Corticosteroids is the mainstay in management. CASE 5: Jlo, 4-year old girl Multidisciplinary approach.  There is no cure for DMD.  CC: muscular dystrophy mimic  Give corticosteroid in the honeymoon period kasi  History nag-iimprove yung bata kasi pagkatapos ng  Frequent falls honeymoon, magiging debilitated na siya.  Birth history was unremarkable  Corticosteroid will slow down the progression of the  Strong family history of thyroid conditions disease.  Physical examination  Severe cognitive delay CASE 4: JJ, 5-year old boy  Short stature  Proximal muscle weakness with hypotonia  CC: unilateral ptosis  Muscle hypertrophy  In the morning or upon waking up, his eyes looked normal  Work up  PE showed unilateral ptosis with mild proximal weakness.  Elevated CK (1000u/L) (other Elevated CK)  CK was normal.  High TSH, Low fT3 & fT4  RNS showed a decremental response. Question and Answer  WHAT IS THE LESION?  Lower motor neuron  WHERE IS THE LESION? Figure 34: Jlo  Muscle  ETIOLOGIC DIAGNOSIS  Thyroid Myopathies  Combination of endocrine and toxic myopathy Figure 33. unilateral ptosis [NEURO3] Araos, Borromeo, Gonzales, Ong, Portic TH Paulino 17 of 20 1.4.04 DISORDERS OF THE LOWER MOTOR NEURON THYROTOXIC PERIODIC PARALYSIS Question and Answer  Gene Defect: Mutation KCNJ18 at Chr.17  WHERE IS THE LESION?  TX. Propranolol and Potassium Supplement  Peripheral Nerve  THYROTOXICOSIS  ETIOLOGY  Thyroxine binds to myofibrils and in excess, impairs  Hereditary Motor-Sensory Neuropathy contractive function  Proximal weakness, wasting + myopathic EMG HEREDITARY MOTOR-SENSORY  Can also induces myasthenia gravis and hypokalemic NEUROPATHIES periodic paralysis  Charcot-Marie-Tooth (Type 1A)  Thyroxine bind to myofibrils in excess, impairs  Most Common type contractile function  Mutation in (PERIPHERAL MYELIN PROTEIN) PMP 22  HYPOTHYROIDISM duplication  Can induce MG in Hypokalemic Periodic Paralysis, the  Gait Disturbance (2y/o), clumsy, falling easily or tripping over latter mainly affecting the east Asian m