neuromuscular diseases radim mazanec, md, ph.d department of neurology
TRANSCRIPT
Neuromuscular Diseases
Radim Mazanec, MD, Ph.D
Department of Neurology
Disorders of the Motor Unit
• Peripheral nerve disorders • Motor neuron disease• Neuromuscular junction disease• Muscle disease
Peripheral Nerve Disorders
• Mononeuropathy– Pattern of weakness and sensory loss
conforms to the distribution of a single nerve• Carpal tunnel syndrome• Peroneal palsy at the fibular head
• Mononeuritis multiplex– Multiple nerves affected in a random pattern
• Acute onset, frequently painful• Diabetes mellitus, vasculitis
• Polyneuropathy (peripheral neuropathy)– Distal, symmetric
Polyneuropathies
• Can affect different types of fibers– Autonomic
– Motor
– Sensory
• Large well myelinated
• Small poorly myelinated or unmyelinated
Symptoms of a Polyneuropathy
• Sensory symptoms– Start in feet, move proximally– Hand sxs appear when LE sxs up to knees– Positive
• Pins and needles• Tingling• Burning
– Negative• Numbness• Deadness• “Like I’m walking with thick socks on”
Exams of peripheral neuropathy
Sensory impairment
akroparesthesias or tactile
hypestesias glove or
sock distribution
Vibration disturbances
pallhypestesia distally (tuning fork C 128 Hz)
Bed side tests
tactile
vibration thermal
myotatic reflexes
Clinical features of polyneuropaties
• Weaknes of LL
• Atrophies of distal muscles
• Deformities pes cavus
• Walk on heels
• Normal muscles strenght at proximal muscles
Diabetic feetandulcerations
AmputationCR 8 000/yGermany 30 000/y
Foot deformity in hereditary neuropathy (CMT disease)
• pes cavus
Classification of Polyneuropathies• By types of fibers involved
– Pure sensory– Sensory motor– Pure motor– Autonomic
• By pathology– Demyelinating– Axonal– Mixed
• By tempo– Acute– Subacute– Chronic
Acute Polyneuropathies
• Guillain Barre Syndrome• Porphyria
– Neuropathy, psychiatric disorder, unexplained GI complaints
• Toxins– Glue sniffing (n-hexane)– Arsenic
Guillain-Barré Syndrom
G Guillain JA Barré A.Strohl
Bulletin de Societe des Medicines Hopitals de Paris,1916;40:1462.
Guillain Barré syndrom from 1927
Guillain Barre Syndrome
• Most common cause of rapidly progressive weakness
• Demyelinating neuropathy• Ascending weakness which may include cranial
neuropathies• Exam reveals symmetric weakness with
areflexia and large fiber sensory loss• Bowel and bladder usually preserved
Guillain Barre Syndrome, cont
• Respiratory failure can be precipitous• Other causes of morbidity and mortality
– Autonomic instability– DVT– Infection
• Immune mediated, may be post infectious• Treatment
– Plasma exchange– Intravenous immunoglobulin
Subacute Polyneuropathies
• Vasculitis– Can be isolated to peripheral nerves or part
of a more systemic process• Paraneoplastic
– May be presenting symptom of the cancer• Chronic inflammatory demyelinating
polyneuropathy– With or without a gammopathy
• Toxins• Drug
Chronic Polyneuropathies
• Metabolic
– Diabetes mellitus
– Chronic renal failure
– Chronic liver failure
– Thyroid disease
• Nutritional
– B12 deficiency
• Infections
– HIV
– Leprosy
• Inherited – Charcot Marie Tooth disease since 1886
Evaluation of a Polyneuropathy
• Lab work• Nerve conduction study/electromyography
– Distinguishes between axonal and demyelinating
– Helps ascertain severity• Nerve biopsy
– Frequently non-diagnostic– Can establish the dx in certain disorders,
such as vasculitis and amyloidosis
Electromyographyfunctional diagnostic method
Conduction studies
Needle EMG
Test of NM transmision
Conduction study of peroneal n.
Conduction study of sural n.
Needle electromyography
Concentric electrode
Myogenic lesion
1 mV
Chronic neurogenic lesion
8 mV
Disorders of the Motor Unit
• Peripheral nerve disorders • Motor neuron disease• Neuromuscular junction disease• Muscle disease
Motor Neuron Disease
• Diseases that can involve Betz cells of the motor cortex, the lower CN motor nuclei, the CST, and/or the anterior horn cells– Amyotrophic Lateral Sclerosis (ALS) – 80%– Progressive bulbar palsy – 10%– Progressive muscular atrophy, spinal
muscular atrophy – 8%– Primary lateral sclerosis – 2%
Dion PA et al.Genetics of motor neuron disorders:new insight into patogenic mechanism.Nature Genetics 2009,10:769-782.
Epidemiology of ALS
ALS (Lou Gehrig´s disease)
Prevalence - 4-6 : 100 000
Incidence - 0.5-3 : 100 000
90-95% sporadic forms of ALS (SALS)• No family history
5-10% familial forms of ALS (FALS)
Classical ALS
First symptoms :
limbs 75% bulbar sy 25%
Upper limbs - 41%
Lower limbs - 34%
ALS – clinical features
• Loss of motor neurons in the cortex, brainstem and spinal cord
• Mix of upper motor neuron and lower motor neuron findings– Weakness, atrophy, fasciculations– Slurred speech, difficulty swallowing,
shortness of breath• Can start in any extremity or the bulbar
musculature• Relentlessly progressive
ALS - prognosis
• 50 % dead in 3 years, 80% dead in 5 years, 5 - 10% live more than 10 years
• Death usually from respiratory failure
Diagnostic algorhitm in ALS
• Clinical symptoms UMN + LMN• Electromyography• MRI brain + C spinal cord• Liquor evaluation (infection)
• Sometimes paraneoplastic exams
Treatment of ALS
• Causative treatment is not available• Neuroprotective treatment
riluzol - inhibitor of glutamate acid
antioxidans – koenzym Q10 + vitamin E
Experimental and clinical studies on more than 200
moleculs – IGF-1, minocycline, creatine ethyl ester,
tamoxifen…
Treatment of ALS
• Symptomatic-paliative treatment – most important today
1. Mobility – -sticks, wheelchair, multifunctional bed2. Nutrition – PEG + Nutrizone3. Communication – tables, books,vocal
communicators, PC4. Anxiety and depresion – antideperesive drugs,
psychotherapy5. Respiration – non-invasive BiPAP or invasive6. Whole family care
Treatment of ALS
• Stem cell therapy – clinical studies are ongoing, including University Hospital Motol (2012-2014 – 30 ALS pts)
• 10 mio per kg
• Systemic aplication i.v.• Intrathecal aplication• Combination i.v. + i.th.• Intraspinal aplication – L spinal cord, later C spinal cord
• Up to date – no EBM data, but in next year – several studies will be finished