Motor Neuron Unit

•Comprised of
•Anterior horn cells & CN motor nuclei
•Peripheral and cranial nerves
•Myo-neural junction
•Muscles
•Practically all disorders of the motor neuron unit are characterized by hypotonia

Definitions
•Tone is the resistance of muscle to stretch
•Two kinds of tone are measured clinically
•Phasic tone is a rapid contraction in response to a high-intensity stretch (examined by testing DTRs)
•Postural tone is the prolonged contraction of antigravity muscles in response to low-intensity stretch
(when depressed, the trunk and limbs cannot be maintained against gravity)

Definitions
•Maintenance of normal tone requires an intact CNS and PNS
•Hypotonia is defined as diminished resistance or resiliency of muscles at rest
•Not surprisingly, hypotonia is a common symptom of neurological dysfunction and is encountered in
diseases of the brain, spinal cord, nerves and muscles
•Hypotonia is not limited to nervous system, various systemic disorders manifest it too
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Approach to Diagnosis
•First step is to determine whether the disease is sited in the brain, spine, or motor unit
•In some disorders, both the CNS and the PNS are involved
•Also, consider non-neurologic reason for the problem
•Systemic illnesses
•Disorders of joints, ligaments, etc

Clues to Motor Unit Disorders

•No malformations of other organs except for joint deformities or maldevelopment of bony structures
•No abnormalities in other brain function
•Absent or depressed tendon reflexes
•Fasciculations and muscle atrophy
•No abnormalities of other organs
•Postural reflexes (TNR, Moro) cannot be superimposed on weak muscles
•Motor unit is the final common pathway of tone; limbs that will not move voluntarily cannot be
moved reflexively

Anatomical Approach to Neuromuscular Diseases

Clues to Diagnosis of Central Hypotonia
•Not difficult from the history and physical examination
•Abnormalities of other brain function (most important)
•Decreased mentation
•Seizures
•Dysmorphic features
•Fisting of hands
•Malformations of other organs
•Movement through postural reflexes
•Normal or brisk DTRs
•Scissoring on vertical suspension

Suprasegmental Conditions: Features

•hypotonia
•normoactive , decreased or increased DTR’s
•normal motor power
•normal EMG
•normal muscle biopsy
•Nonspecific mental deficiency
•Hypotonic cerebral palsy
•Birth trauma, hemorrhage, hypoxia
•Chromosomal disorders
•Metabolic, Nutritional and Endocrine Disorders
•Congenital Heart Diseases

Anterior Horn Cell Disorders

Congenital
Spinal Muscular Atrophy
●Infantile Spinal Muscular Atrophy
●Intermediate Spinal Muscular Atrophy
●Juvenile Muscular Atrophy
Acquired
●Poliomyelitis
●Botulism
Spinal Muscular Atrophy TYPE I
•Type I SMA also known as Werdnig-Hoffman or Progressive Infantile SMA
•Progressive loss of AHC & CN motor nuclei
•Autosomal recessive disorder
•Onset is in first 6 months – may begin in utero
•Presentation
•Poor tone
•Feeding difficulties
•Respiratory distress

•Findings on Exam
•General symmetric weakness
•Loss of DTRs
•Muscle atrophy
•Fasciculations - especially the tongue
•Congenital contractures and hip dislocations
•Frog-leg posture on supine
•Bell-shaped deformity of chest

SMA TYPE I - Werdnig-Hoffman Disease

Spinal Muscular Atrophy

•Diagnosis
•EMG will show fibrillations
•Muscle biopsy-fascicules with atrophic fibers
•Treatment
•No specific treatment
•Genetic counseling
•Prognosis
•The earlier the symptoms, the more progressive the disease
•Death usually <3 y due to respiratory paralysis and infection

Intermediate Severity Spinal Muscular Atrophy

•Starts manifesting above 6 months od life
•able to sit unaided but not able to stand or walk
•tremors of the hand
•normal intellect
• live up to adolescene or adulthood
•respiratory problems if intercostals are affected
Kugelberg-Welander Disease
•AKA: Juvenile Spinal Muscular Atrophy
•Autosomal recessive
•Onset between 2 and 17 years (mean: 9 years)
•Legs weaken before arms; proximal weakness
•Gowers sign
•Slowly progressive with loss of ambulation 8-9 years after diagnosis

Kugelberg-Welander Disease

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Paralytic Poliomyelitis
•Caused by a single-stranded RNA enterovirus
•Less than 10% of those infected will have neurologic findings
•Virus infects and destroys the anterior horn cells
•Virus infects through respiratory secretions and fecal contamination

Paralytic Poliomyelitis
•Initial Presentation
•First with fever, malaise, headache
•Progresses to nausea, vomiting, anorexia, diarrhea
•Classic triad: fever, muscle spasm and nuchal signs
•Eventual progression to neurologic signs

Paralytic Poliomyelitis
•Neurologic signs
•Loss of muscle strength usually sudden with complete loss of function within hours to days
•Characteristically asymmetric with greater weakness in the legs than the arms
•Decreased to absent deep tendon reflexes

Paralytic Poliomyelitis
•Diagnosis
•Consider in non-immunized infant or during outbreaks
•Virus must be isolated from throat, stool or CSF
•Treatment
•Supportive
•Prognosis
•Loss of function is prominent
Peripheral Neuropathies
A. Demyelinating-motor conduction velocity is markedly slowed to half the normal rate
ex. Infectious polyneuritis,peroneal muscular atrophy, leucodystrophies
B. Axonal-conduction velocity may be normal or only slightly depressed
ex. Toxins,diabetes,porphyria

Peripheral Neuropathies
A. Hereditary

B. Acquired

Guillain-Barre Syndrome
•Also known as Inflammatory polyradiculoneuropathy
•Usually occurs within 4 weeks of a non-specific infection (URI or gastroenteritis)
•Has been associated EBV, Coxsackie, Influenza, CMV, Mycoplasma, Campylobacter, and
immunizations

Guillain-Barre Syndrome
•Etiology
•Autoimmune attack of the motor neuron causing segmental demyelination – especially of the
rootlets and proximal nerves
•Variant – axonal degeneration

Guillain-Barre Syndrome
•Clinical Findings
•Progressive symmetric ascending motor weakness ranging from mild weakness to paralysis
•Numbness and paresthesias of the hands and feet
•Sensory loss – especially proprioception and vibratory sensation
•Frequent autonomic findings: flushing, erratic heart rate and BP

Guillain-Barre Syndrome
•Diagnosis
•Often clinical: as a rule, there must be progressive motor weakness of more than one extremity with
areflexia
•Elevated CSF protein with no cellular reaction (“albumino-cytologic” dissociation)
•Electrophysiologic studies will show slowing of the nerve conduction velocities

Guillain-Barre Syndrome
•Treatment
•Supportive: 20% will need respiratory support
•Steroids have not been proven useful
•Plasmapheresis significantly shortens the duration of symptoms
•IVIG (400 mg/kg/day for 4 days, or 2g/kg as a single dose) is quickly becoming the treatment of
choice

Guillain-Barre Syndrome
•Course
•Monophasic disease
•Maximum disability usually after 1 week of onset
•1-3 week period of stability
•Recovery anywhere from 6-8 months but can take several months
•Rarely with residuals

Miller-Fisher Syndrome
•Variant of G-B syndrome vs. Brainstem encephalitis
•Characterized by:
•Ataxia
•Ophthalmoparesis (especially vertical gaze palsy)
•Areflexia
•Prognosis is excellent

Myasthenia Gravis
•Autoimmune attack on the acetylcholine receptors
•Antibodies bind to these receptors preventing generation of the end plate potential
•Usually seen in children >10 years, but can be as young as <2 years
•More common in girls

Neuromuscular Junction
Myasthenia Gravis: Types

1.Transient Neonatal-infants of myasthenic mothers,limp with genralized hypotonia,difficulty in

sucking and swallowing, ptosis and facial weakness, lasts for 2-4 weeks
2. Congenital or Infantile-non-myastenic mothers,onset after the neonatal period, usually within the
1st 1-2 years of life,weak cry, grunting,generalized weakness,respiraory difficulties
3. Juvenile-onset between 2- 20 yrs, ptosis with or without opthalmoplegia,weakness particularly at
the end of the day

Myasthenia Gravis
•Presentation
•50% of newly diagnosed cases present with ocular weakness (ptosis and diplopia)
•25% present with bulbar findings
•25% present with extremity weakness
•Key to Diagnosis –
○Fatigability

Myasthenia Gravis
Myasthenia Gravis
•Diagnosis
•History – weakness towards end of the day
•Edrophonium chloride (Tensilon) test: a short-acting anti-acetylcholinesterase.
●Positive response: Marked but short-lived improvement in weakness
•EMG: electrodecremental response
•Antibody testing: + in 90% of patients
•Chest CT scan

Chest radiograph and CT

Thymoma

Myasthenia Gravis
•Treatment
•Cholinesterase inhibitors (neostigmine and pyridostigmine)
•Thymectomy: Thymus sensitizes lymphocytes to produce the antibodies
•Steroids
•Immunosuppresants

Myasthenia Gravis
•Prognosis
•Complete or partial remission in 25% within 2 years
•80% improve post-thymectomy
•Most others have chronic remissions and exacerbations

Neonatal Myasthenia Gravis

•Maternal antibodies to the acetylcholine receptor cross the placenta
•Only 10% of infants born to mothers with myasthenia will be symptomatic
•Total resolution by 6 weeks as the antibodies are cleared

Infantile Botulism
•Caused by the exotoxin produced by C. botulinum, an anaerobic bacillus
•Spores are ingested by the neonate and flourish if the gut has not been colonized by normal flora
•Only 20% is linked to spores in honey
•Usually diagnosed between 5 and 12 weeks of age
•Exotoxin irreversibly blocks release of Ach

Infantile Botulism
•Presentation
•First sign is often constipation
•Followed by ocular findings (ptosis) and bulbar signs (feeding difficulties)
•Weakness is progressive, descending, flaccid

Infantile Botulism
•Diagnosis
•EMG: slow rate will give smaller amplitude, faster rate will give larger amplitude, these findings are
not very sensitive
•Must isolate the toxin in the stool or blood

Infantile Botulism
•Treatment
•Supportive – approximately 50% require ventilatory assistance, often done prophylactically to avoid
aspiration and maintain airway patency
•Antitoxin does exist, but it is horse-serum derived and therefore not safe

Infantile Botulism
•Prognosis
•Without complications, total recovery is the rule!
•Must wait for nerves to regrow terminal portions – may take up to a year, but average hospital stay
is approximately 1 month

Other Types of Botulism

•Food-borne
•Much more common in places at higher elevations due to lower boiling point of water
•Wound
•Grows in “dirty” wounds and releases exotoxin
•Aggressive treatment with antibiotics and the horse-serum derived antitoxin

Muscle Disorders
•Muscular dystrophies
•Myotonic dystrophies
•Metabolic myopathies
•Congenital myopathies

Congenital Myopathies
•Developmental disorders of skeletal muscles
•Main clinical feature is infantile hypotonia and sometimes arthrogryposis
•Diagnosis is established only by muscle biopsy
•Some are associated with cerebral anomalies and cerebellar hypoplasia

Congenital Myopathies
B.Structural
•Central core disease
•Minicore disease
•Nemaline myopathy
•Mitochondrial myopathies

Congenital Myopathies
A.Metabolic /Endocrine Myopathies
•Inborn errors of metabolism
•Thyroid disorders
•Pituitary and adrenals
•Nutritional myopathies
Duchenne Muscular Dystrophy
•X-linked recessive defect in dystrophin gene, although up to 30% are new mutations
•Muscles have <3% dystrophin
•Absence of dystrophin results in a membrane defect, which causes leakage of cytoplasmic contents
and influx of calcium leading to eventual muscle necrosis

Duchenne Muscular Dystrophy

•Carrier State
•90% of female carriers are asymptomatic
•Other carriers have varying degrees of the disease
•Remember your Lyon hypothesis

Duchenne Muscular Dystrophy

•Clinical Findings
•Gowers sign – classic example of proximal muscle weakness
•Trendelenburg gait: waddling gait with lumbar lordosis
•Calf hypertrophy, sometimes the tongue is also hypertrophied
•Intellectual impairment: Only 20%-30% have IQs >75

Duchenne Muscular Dystrophy

•Clinical Course
•First symptoms usually around 3-4 years
•Frequent toe-walking
•As weakness progresses, heel cords tighten leading to loss of ambulation usually around age 10
•Kyphoscoliosis then progresses rapidly leading to respiratory compromise
•All eventually develop some degree of cardiomyopathy

Gowers Sign

Duchenne Boys

Duchenne Muscular Dystrophy

•Diagnosis
•Muscle biopsy shows necrosis and muscle fibers in varying degrees of degeneration
•Laboratory: Elevated LDH, AST, and especially CK
•Prognosis
•Death usually by 18 y secondary to respiratory failure, CHF or pneumonia

Becker Muscular Dystrophy

•Same gene locus as Duchenne, but has a much milder, more protracted course
•Muscles have >3% but <20% dystrophin
•Usually remain ambulatory until late adolescence
•Death often postponed until the late 20’s

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Myotonic Dystrophy
•Also known as Steinert disease
•Autosomal dominant – usually inherited from the mother
•Multisystem disease
•Muscles (myotonia to atrophy)
•Heart (dysrhythmias)
•Brain (mental retardation)
•Eyes (cataracts)
•Gonads (hypogonadism, azospermia)

Myotonic Dystrophy
•Usual age of onset: Adolescence on
•Can present at birth with severe hypotonia, facial weakness, respiratory distress, hip dislocation and
clubbed feet
•Distal>proximal weakness
•Myotonia (grip, percussion of thenar eminence and tongue)

Myotonic Dystrophy
•Diagnosis
•Relatively easy with typical facies, myotonia and other characteristics
•EMG – myotonic discharges with dive-bomber sound
•Treatment
•No specific
•Quinidine, phenytoin, carbamazepine, procainamide may be tried in severe myotonia
•Genetic counseling

Myotonic Dystrophy

Dermatomyositis
•Unknown cause, likely multifactorial
•Viral connections – Coxackie is main suspect
•Genetic predisposition
•Rare before age 2 years, average onset 8-9 years
•Girls are more often affected with a ratio of 3:2

Dermatomyositis
•Clinical Findings
•Weakness is generally seen first in proximal muscles of extremities and trunk
•Gowers sign
•Affected muscles are often stiff, indurated and tender
•Heliotrope rash – violaceous in butterfly distribution

Dermatomyositis Rash

Dermatomyositis
•Other Findings
•Arthritis, lymphadenopathy, fever, hepatosplenomegaly
•Calcinosis in 20% to 50%
•GI: dysphagia, abdominal pain, constipation, melena, performation
•Extensor surfaces of joints become erythematous, atrophic, scaly
•Knuckles: Gottron papules

Calcinosis in Dermatomyositis

Gottron Papules

Dermatomyositis
•Diagnosis
•Usually clinically
•EMG
•Rheumatoid factor usually negative
• Antinuclear antibodies
•Sedimentation rate: Normal to high
•Increased CK, AST, LDH, aldolase

Dermatomyositis
•Treatment and Prognosis
•Steroids – initially high dose, then tapered while following enzymes
•Good prognosis in children
•With treatment, most are pushed into remission
•Some cases may be chronic, smoldering
•Some have severe, crippling contractures

Diagnosis
•History and physical/neurological examination
•Muscle enzymes
•NCV and EMG
•Peripheral nerve biopsy
•Muscle biopsy

Summary
•Hypotonia may arise from CNS (most common), PNS and other systemic diseases
•Investigations depend upon physical and neurological findings
•Some are treatable, many are progressive and some are genetically determined