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