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NEUROMUSCULAR DISORDERS

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Title: NEUROMUSCULAR DISORDERS


1
NEUROMUSCULAR DISORDERS
  • Dr Fawale MB

2
Neuromuscular Disorders
  • Peripheral Nerve disease (neuropathies)
  • Neuromuscular junction diseases
  • Primary muscle diseases (myopathies)

3
PERIPHERAL NERVE DISEASE
4
Definitions
  • Peripheral nerves
  • All neural structures outside the pial membrane
    of the spinal cord and brainstem
  • Cranial nerves, 10 pairs (optic and olfactory
    nerves are excluded)
  • Spinal nerves, 31 pairs
  • Peripheral neuropathy
  • A syndrome resulting from disease of the
    peripheral nerve of any cause

5
Peripheral nerves - Structure
  • Cells
  • Anterior horn (motor)
  • Dorsal root ganglia (sensory )
  • Intermediolateral gray of spinal cord
    (Autonomic)
  • Axons
  • Motor
  • Sensory
  • Autonomic

6
Peripheral Nerves - Structure
  • Myelin
  • Schwann cells
  • Endoneurium,
  • perineurium,
  • and epineurium
  • Blood vessels

7
Nerve Fiber Types
8
Peripheral Neuropathy - Classification
  • Topographic/clinical pattern
  • Radiculopathies, Plexopathies, Mononeuropathy,
    polyneuropathy, mononeuritis multiplex
  • Mode of onset
  • acute, subacute, chronic
  • Fibre type
  • motor, sensory, autonomic, mixed
  • Fibre size
  • Large, small
  • Pathologic process
  • axonal, demyelinating, mixed
  • Aetiology
  • Infectious, paraneoplastic, metabolic, vascular,
    toxic, inflammatory, genetic
  • Distribution
  • symmetric, asymmetric, cranial, spinal, proximal,
    distal

9
Symptoms and signs
  • Motor
  • Sensory
  • Positive phenomena
  • Negative phenomena
  • Autonomic
  • Deformities Trophic changes

10
Symptoms and signs - Motor
  • Weakness, paralysis
  • Usually starts diatally
  • Propotional to the number of neurons lost
  • Wasting, Atrophy
  • Evident in axonal but not in demyelinating
    disease
  • Hypotonia/atonia
  • Hyporeflexia/areflexia
  • Usually when large fibres are affected
  • Fasciculation
  • May be induced by exercise or percussion
  • Myokymia, Cramps, Spasms

11
Symptoms and signs - Motor
  • Hypotonia/atonia
  • Hyporeflexia/areflexia
  • Atrophy
  • Fasciculation

12
Symptoms and signs - Motor
  • Wasting of the small hand muscles in a chronic
    neuropathy

13
Symptoms and signs - sensory
  • Positive sensory phenomina
  • Often the 1st sign of neuropathy
  • Large fibre disease
  • Paresthesias
  • Spontaneous sensations without stimulation
  • tingling, prickling (pins and needles),
    formication, and sensations of tension, pressure,
    and swelling
  • Small fibre disease
  • Hyperalgesia
  • Threshold to pain appears lowered, more pain than
    normal upon noxious stimulation

14
Symptoms and signs - sensory
  • Positive sensory phenomina
  • Dysesthesias
  • Altered sensation
  • provoked, abnormal, painful sensation
  • Hyperpathia
  • Elevated pain treshold but once reached,
    sensation to painful stimulus is exaggerated
  • Allodynia
  • Painful response to non-noxious stimulation
  • Causalgia
  • Burning pain in the distribution of the nerve
  • Due to nerve trauma

15
Symptoms and signs - sensory
  • Negative sensory phenomina
  • Large fibre
  • Loss of touch
  • hands feel like cotton wool, numbness
  • difficulty discriminating textures
  • Loss of JPS
  • unsteadiness in the dark -gt sensory ataxia
  • ve Rombergs test
  • Small fibre
  • Loss of pain temperature sense
  • Neuropathic ulcers/burns

16
Symptoms signs - sensory
17
Symptoms and signs - sensory
18
Symptoms and signs - Autonomic
  • Sudomotor
  • dry skin, lack of sweating, excessive sweating
  • Pupillary
  • Poor dark adaptation, sensitivity to bright
    lights
  • Cardiovascular
  • Postural light-headedness, fainting, orthostatic
    hypotension
  • Urinary
  • urgency, incontinence, dribbling
  • Gastrointestinal
  • nocturnal diarrhea, constipation, vomiting of
    retained food
  • Sexual
  • erectile impotence and ejaculatory failure in
    men, loss of ability to reach sexual climax in
    women

19
Symptoms and signs
  • Deformities Trophic changes
  • Extremities
  • Cold blue extremities
  • Cutaneous hair loss
  • Brittle finger/toe nails
  • Neuropathic joint (Charcots joint)
  • Talipes equinus, claw foot
  • Spine
  • Kyphoscolios

20
Symptoms and signs
  • Deformities Trophic changes
  • Pes cavus, with clawing of the toes in a patient
    with familial neuropathy

21
Diagnosis
  • Clinical manifestations (symptoms/signs)
  • Electrophysiology
  • Blood and urine studies
  • Imaging (hypertrophic nerves)
  • Cerebrospinal fluid (protein elevation)
  • Biopsy nerve/skin/muscle/marrow/other

22
Important Causes of PND
23
Diabetic Neuropathy
  • Seen in 10-65 of all patients with diabetes
  • Present in 7.5 of patients at diagnosis
  • ½ have distal symmetric polyneuropathy
  • ¼ have compression or entrapment neuropathies
    (mainly carpal tunnel syndrome)
  • Risk factors
  • Poor glycaemic control, long duration of disease
  • Age, height, male gender, alcohol, smoking,
    hyperlipidaemia, hypertension

24
Diabetic Neuropathy - Clinical Classification
  • Symmetric
  • Distal symmetric polyneuropathy (DSP)
  • Diabetic autonomic neuropathy (DAN)
  • Painful distal neuropathy with weight loss,
    ?diabetic cachexia?
  • 4. Insulin neuritis
  • 5. Polyneuropathy after ketoacidosis
  • 6. Polyneuropathy with glucose impairment
  • 7. CIDP in DM

25
Diabetic Neuropathy - Clinical Classification
  • Asymmetric
  • Radiculoplexus neuropathies (DRPN)
  • Lumbosacral (DLRPN)
  • Thoracic (DTRN)
  • Cervical (DCRPN)
  • Mononeuropathies
  • Median neuropathy at the wrist (carpal tunnel
    syndrome)
  • Ulnar neuropathy at the elbow
  • Peroneal neuropathy at the fibular head
  • Cranial neuropathies

26
Diabetic Neuropathy - Symmetric
  • Distal symmetric polyneuropathy
  • Most common diabetic neuropathy
  • Chronic symmetric symptoms involving the distal
    extremities
  • Peripheral nerves involvement in a
    length-dependent pattern with the longest nerves
    affected first
  • Sensory, motor, and autonomic, sensory
    predominating

27
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28
Diabetic Neuropathy - Symmetric
  • Diabetic autonomic neuropathy
  • Pure autonomic neuropathy is rare
  • Painful distal neuropathy with weight loss
    (?diabetic cachexia?)
  • precipitous and profound weight loss followed by
    severe pain worse at night. Usually over months
  • not related to duration or severity of DM

29
Diabetic Neuropathy - Asymmetric
  • Cranial mononeuropathy
  • Common nerves involved - III, IV, VI, VII II
  • CN III, IV, VI
  • Acute/subacute unilateral periorbital pain or
    headache followed by diplopia
  • Typically pupil sparing (occurs in 14-18)
  • Complete spontaneous recovery within 3 months

30
Diabetic Neuropathy - Asymmetric
  • CN VII
  • acute or subacute (taste often not involved)
  • Recurrent or bilateral
  • Spontaneous recovery in 3-6 months usual
  • CN II
  • In form of anterior ischemic optic neuropathy
  • acute visual loss or visual field defects
  • Optic disk pale and swollen, flame-shaped
    hemorrhages

31
Diabetic Neuropathy - Asymmetric
  • Somatic mononeuropathies
  • Common sites
  • Median nerve at the wrist (carpal tunnel
    syndrome)
  • Ulnar nerve at the elbow
  • Common peroneal nerve at the fibular head
  • Infarction -gt Acute focal pain, weakness, sensory
    loss
  • Mechanisms
  • Entrapment or compression where it crosses
    common pressure points
  • Ischemia and subsequent infarction

32
Diabetic Neuropathy - Asymmetric
  • Diabetic Radiculoplexus Neuropathy
  • DLRPN
  • Sudden, asymmetric, and unilateral onset proximal
    gt distal
  • Pain initially -gt weakness, wt loss
  • recovery is incomplete and delayed
  • High CSF protein ESR, ve RF ANA
  • DTPN
  • Band-like sensation, protuberance of abdomen, wt
    loss in gt 50

33
Diabetic Neuropathy - Pathophysiology
  • Not completely understood
  • Generally is accepted as a multifactorial process
  • Multiple hypotheses have been advanced
  • Metabolic theory
  • Vascular (ischemic-hypoxic) theory
  • Altered neurotrophic support theory
  • Laminin theory
  • Autoimmune theory

34
Diabetic Neuropathy Pathophysiology Metabolic
Theory
35
Diabetic Neuropathy Pathophysiology Metabolic
Theory
  • Hyperglycemia
  • Activity of the polyol pathway
  • Sorbitol accumulation
  • Osmotic damage
  • Myoinositol depletion
  • Decreased membrane Na/K-ATPase activity,
  • Impaired axonal transport

36
Diabetic Neuropathy Pathophysiology
  • Altered neurotrophic support theory
  • Impaired production and transport of NGF
  • Survival
  • Laminin theory
  • Lack of normal expression of laminin beta 2 gene
  • Autoimmune theory
  • Immunogenic alteration of the endothelial
    capillary
  • Vascular (ischemic-hypoxic) theory
  • Hyperglycemic
  • Increased endoneurial vascular resistance
  • Endoneurial ischemia
  • AGEPs
  • Capillary damage
  • Axonal transport
  • Na/K-ATPase activity,
  • Axonal degeneration.

37
Diabetic Neuropathy Staging
  • NO - No neuropathy
  • N1a - Asymptomatic neuropathy detected as nerve
    conduction abnormality in at least 2 nerves
  • N1b - N1a and abnormal neurologic examination
  • N2a - Symptomatic mild diabetic polyneuropathy
    sensory, motor, or autonomic symptoms patient
    able to heel walk
  • N2b - Severe symptomatic diabetic polyneuropathy
    (as in N2a, but patient unable to heel walk)
  • N3 - Disabling diabetic polyneuropathy

38
Diabetic Neuropathy Treatment
  • General measures
  • More frequent follow-up care
  • Education on foot care
  • If necessary, a podiatry referral
  • Current treatments
  • Glycemic control
  • TCAs
  • AEDs
  • CZP, PHT, gabapentin, lamotrigine,
  • Lidocaine gel or tape
  • Mexiletine (similar to lignocaine) orally
  • Capsaicin topical
  • Acupuncture, Spinal cord stimulation, TENs
  • Emerging therapies
  • Aldose reductase inhibitors
  • alrestatin, sorbinil, tolrestat
  • Alpha-lipoic acid
  • Gamma-linolenic acid
  • NGF

39
Guillain-Barre syndrome
  • An acute-onset, immune-mediated
    polyradiculoneuropathypathy
  • Epidemiology
  • Incidence 2/15,000 cases
  • Who Peak incidence in 2nd decade of life, MF
  • No predilection for social class
  • Where Occurs all over the world
  • When Non-seasonal and non-epidemic
  • Risk factors Antecedent illness in 50 of
    patients - URTI, GIT, post surgery, vaccination,
    parturition
  • Organisms - Campylobacter jejuni, EBV, CMV, HIV,
    Mycoplasma pneumonia, influenza virus

40
Guillain-Barre syndrome - Clinical Variants
  • Acute inflammatory demyelinating
    polyradiculoneuropathy
  • Acute motor axonal neuropathy (AMAN) (antiGD1)
  • Acute motor and sensory axonal neuropathy
  • Acute Panautonomic Neuropathy

41
GBS - Clinical Variants
  • Regional
  • Fisher syndrome (antiGQ1b)
  • ophthalmoplegia, ataxia, and areflexia
  • Cervico-brachial-pharyngeal
  • often with ptosis
  • Oculopharyngeal weakness
  • Predominant paraparesis
  • Bilateral facial or abducens weakness with distal
    paresthesias
  • Ophthalmoplegia with GQ1b autoantibodies

42
GBS - Pathogenesis-Demyelination
Myelin
Antibodies
43
GBS - Pathogenesis-Demyelination
44
GBS - Clinical features
  • Sensory
  • Lumbar or interscapula pain, limb paraesthesia
  • Sensory examination often normal
  • Motor weakness
  • Distal onset, ascending character
  • Acute onset, progressive illness, monophasic
    course
  • Reaches a clinical nadir by 2-4wks
  • Areflexia, atonia
  • Diaphragmatic weakness, oropharyngeal weakness
  • CN palsies
  • Autonomic
  • 50of patients
  • Tarch, arrhythmias, hypotension, hypertension, GI
    dysmotility, bladder atony

45
GBS - Workup
  • CSF protein cells
  • Normal opening pressure
  • Cytoalbuminergic dissociation
  • occurs in over 90 of patients at clinical nadir
  • May be normal initially
  • No association between protein level clinical
    severity
  • If gt50 WBC/mL consider differentials
  • Nerve Conduction Studies (NCS)
  • Most important diagnostic test

46
GBS - Workup
  • ECG cardiac monitoring
  • Autonomic tests
  • Antiganglioside abs (IgG)
  • seldom beneficial in classic AIDP
  • can help with variants
  • Full blood count - normal
  • EU, Cr SIADH in 40
  • Blood culture
  • Serology - HIV, EBV, CMV, Borrelia, VZV, Polio
  • Urine
  • heavy metals
  • Porphyrin metabolism products
  • Stool MCS, Botulinum
  • Throat swab MCS, viral
  • MRI spine
  • CXR
  • Nerve biopsy

47
GBS - Treatment
  • Hospital admission for close monitoring
  • Specific - Immunotherapy
  • Plasma exchange (PE)
  • IV immunoglobulin (IVIg)
  • Supportive

48
GBS Immunotherapy
  • The effects of PE and IVIg are equivalent
  • PE IVIg no added advantage.
  • Corticosteroids not beneficial . not
    recommended.
  • Interferon beta - significant improvement
  • Adult Doses
  • IVIg - 0.4 g/kg/day x 5 days
  • Plasma exchange - typically 5 plasma volumes over
    12 weeks
  • IVIg has become the treatment of choice due to
    ease of administration.

49
GBS Supportive Care
  • Up to 25 require ventilatory support . ICU
    care.
  • Indications for ICU care
  • Vital capacity lt20mg/kg or rapidly deteriorating
  • Rapidly progressive tetraparesis
  • Severe bulbar palsy
  • Severe autonomic cardiovascular instability
  • Monitoring during acute phase
  • Temp, Pulse ,BP, RR
  • Vital capacity,
  • Pupils , GCS,
  • Cough ,Swallow, Pain
  • Urine output
  • ECG if dysautonomia

50
GBS Supportive Care
  • Prophylaxis against thromboembolism
  • GI prophylaxis - H2-blocker
  • Enteric nutrition
  • Constipation - enemas.
  • Ileus (rare) - bowel rest parenteral nutrition
  • Analgesics
  • Physiotherapy
  • Tarchycardia
  • Symptomatic bradycardia - Atropine
  • Hypertension - short-acting beta-blocker or
    nitroprusside.
  • Hypotension IVF supine positioning.
  • Second-degree and Third-degree heart block-
    temporary pacing

51
GBS Differentials Prognosis
  • Poor prognostic Indices
  • rapid progression of symptoms,
  • advanced age,
  • prolonged ventilation (gt1 mo)
  • severe reduction of action potentials on
    neuromuscular testing.
  • Full recovery may be expected in 50-95 of cases
  • Mortality 5-10
  • Differentials
  • Transverse myelitis
  • Brain stem encephalitis
  • Metabolic myopathies
  • Polymyositis
  • Lead poisoning
  • Intermittent porphyria
  • Hysteria

52
Chronic inflammatory demyelinating neuropathy
  • Underdiagnosed, potentially treatable disease
  • Immune-mediated pathogenesis
  • Characterized by symmetrical weakness in both
    proximal and distal muscles
  • Impaired sensory functions
  • Absent or diminished DTR
  • Progressive illness with duration greater than 2
    months course could be relapsing (in the young)
    or chronic
  • Elevated CSF protein
  • Electrophysiological evidence of demyelination

53
Chronic inflammatory demyelinating neuropathy
  • Treatment
  • IV Immunoglobulin
  • Plasma exchange
  • Steroids
  • - 60-80 recovery
  • Others
  • Azathioprine/Cyclophosphamide/Cyclosporin
  • Interferon beta 1a

54
Nutritional Polyneuropathy
  • Beriberi
  • Thiamine deficiency
  • Note nutritional polyneuropathy is not limited to
    thiamine deficiency
  • The heart and peripheral nerves may be affected
    together or separately
  • Cardiac features
  • Tachycardia, exertional dyspnea, heart failure

55
Pathology
  • Axonal degeneration
  • Segmental demyelination may also be seen in a few
    fibres
  • Distal parts of the longest myelinated fibres are
    most affected
  • Chromatolysis of dorsal root ganglion cells
  • Degeneration may be seen in dorsal column
  • Vagus and phrenic nerves, and sympathetic trunks
    may be affected

56
Clinical features
  • Lower limbs usually affected first
  • Symptoms usually insidious, but may be rapidly
    progressive
  • Loss of muscle stretch reflexes
  • Sensory loss
  • All modalities
  • Paresthesiae
  • Heat and burning sensations
  • Pain
  • Dull aching, or lancinating pain
  • Weakness
  • Atrophy
  • Cramping and tightness of muscles
  • Foot and wrist drop

57
Treatment
  • Vitamin B replacement
  • General improvement of diet
  • Anticonvulsants for dysesthesiae
  • Prevent contractures

58
Vasculitic neuropathies
  • Pathology
  • Vasculitis of vasa nervorum
  • Etiology
  • SLE, Rheumatoid arthritis, Systemic sclerosis,
  • Lyme disease, HIV - AIDS
  • Presentation
  • Mononeuritis multiplex

59
Toxic polyneuropathies
  • Thallium, arsenic, organophosphates
  • Thallium
  • May present like Gullain- Barre syndrome or acute
    sensory polyneuropathy
  • If intake of Thallium salts is oral, abdominal
    pain, vomiting, and diarrhoea may be present
  • Loss of muscle stretch reflexes
  • Sensory loss and ataxia
  • Cranial nerve palsies

60
Organophosphate poisoning
  • Over 20 000 compounds are designated as
    organophosphates
  • Tri-esters of phosphoric acids are the most
    common
  • They may be solids, liquid, or gases
  • Nerve gases
  • Sarin
  • Tabun
  • Insecticides
  • Parathion
  • Malathion

61
Organophosphate poisoning
  • OPs interact with esterases and proteases
  • Esterases
  • A type, hydrolyses OP
  • B type, inhibited by OP
  • OPs phosphorylates B esterases
  • Reactivation is very slow or does not occur
  • Absorption through the skin, GIT, respiratory
    tract
  • Clinical syndromes of poisoning
  • Acute
  • Delayed

62
Clinical features of acute syndrome
  • Muscarinic
  • Lacrimation, salivation, sweating, bronchorrhea,
    miosis, bronchoconstriction, abdominal cramps,
    diarrhoea, bradycardia
  • Nicotinic
  • Muscular weakness, fasciculations, tachycardia,
    hypertension
  • Central
  • Anxiety, confusion, blurred vision, tremor,
    convulsions, respiratory depression, coma

63
Treatment
  • Atropine 1-5 mg i.v. Every 10 -30 mins. Dose
    should be titrated against pupil size, heart rate
    and dry skin.
  • Pralidoxime 1 gm i.v. over 30 mins, 8 -12 hrly

64
Clinical features of delayed syndrome
  • Organosphosphate induced delayed polyneuropathy
  • Sensorimotor axonopathy
  • OPs attack neuropathy target esterase, NTE, which
    is present in neurons.
  • Triorthocresyl phosphate,TOCP, is commonly
    implicated
  • Epidemics have occurred, Ginger-Jake paralysis

65
Clinical features of delayed syndrome
  • Symptoms develop 1-4 weeks after after single
    dose
  • Cramping of muscles
  • Distal numbness and paresthesias
  • Progressive leg weakness
  • Loss of tendon reflexes
  • Motor features predominate
  • Quadriplegia in severe cases
  • No specific treatment

66
Drug induced polyneuropathies
  • Isoniazid
  • Symmetrical numbness and tingling of the toes and
    feet
  • Burning pain, and sensory loss
  • Weakness of distal muscles of the legs
  • Loss of muscle stretch reflexes
  • INH interferes with pyridoxine metabolism,
    inhibition of phosphorylation of pyridoxine
  • Pyridoxine, 150-450 mg dly is preventive

67
Antineoplastic Agents
  • Cisplatin
  • A platinum compound
  • Interferes with axonal transport
  • Sensory polyneuropathy
  • Gait ataxia
  • Taxoids
  • Paclitaxel and docetaxel are diterpene alkaloids
  • Prevents disassembly of microtubules
  • Sensory polyneuropathy

68
Antineoplastic Agents
  • Vincristine
  • A vinca alkaloid
  • Blocks polymerisation of microtubules
  • Sensory polyneuropathy

69
Leprosy
  • Commonest cause of multiple mononeuropathy
  • M. leprae affects skin and peripheral nerves
  • Both major forms associated with neuropathy
  • Tuberculoid leprosy
  • good immune response, confinement of organisms to
    small patches of skin and associated nerves
  • Hypopigmented, anaesthetic macules, anhydrosis,
    Thickened nerves (post. auricular, digital,
    sural, radial, ulna, peroneal)

70
Leprosy
  • Lepromatous type
  • diminished immunity, widespread distribution of
    organisms and lesions
  • sensory polyneuropathy pain temp.
  • associated resorption of digits, trophic ulcers,
    cyanosis, anhydrosis
  • Treatment Dapsone, Rifampicin, Clofazimine,
    Roxithromycin
  • Reactions in Leprosy Erythema nodosum, acute
    neuritis

71
Leprosy
72
Neuropathies in HIV infection
  • Distal symmetrical polyneuropathy
  • painful sensory type/sensorimotor
  • Inflammatory demyelinating polyneuropathy
  • Mononeuritis multiplex
  • CMV Herpes zoster radiculoneuropathy
  • Cranial neuropathy
  • Autonomic neuropathy
  • Drug-induced/nutritional neuropathy

73
Hereditary Neuropathies
  • Charcot-Marie-Tooth disease (HSMN -1)
  • Slowly progressive demyelinating neuropathy
  • Heterogenous group of disorders affecting
    peripheral nerves and anterior horn cells
  • Associated with Chromosone 5, 8, 11, 17
  • Sporadic or familial (dominant/recessive)
  • HSMN II Axonopathy
  • HSMN III Dejerine-Sottas disease (raised CSF
    protein , slowed nerve conduction)

74
HSMN -1 Features
  • Distal muscle wasting
  • Inverted champagne bottle
  • Onset in adulthood ( age lt 30 years)
  • Wasting and weakness of peroneal, tibial muscles
  • Involvement of distal upper limbs
  • Pes cavus 75
  • Palpable nerves 25
  • Associated ataxia and tremor 10

75
Charcot-Marie-Tooth Disease
76
Facial nerve palsy
  • Nucleus
  • Pons
  • Infranuclear components
  • Branchiomotor
  • GVE, parasympathetic from superior salivatory
    nucleus
  • Ganglia, pterygopalatine, submandibular
  • SVA, taste fibres from anterior 2/3 of tongue
  • Ganglia, geniculate
  • GSA, cutaneous sensation from anterior wall of
    external auditory canal

77
Functional anatomy of VII Nerve
78
Bells Palsy
  • Most common disease of the facial nerve
  • General features
  • MF
  • Median age of onset 40 years, but may occur at
    any age
  • Occurrence low lt 10 years of age
  • Right and left side of the face equally affected

79
Bells Palsy
  • Clinical features
  • Acute onset
  • Maximum paralysis within 48 hours
  • Impairment of taste
  • Hyperacusis
  • 80 of subjects recover fully within
  • a few weeks to two months
  • Early recovery is good prognostic sign
  • Etiology
  • Viral agents possible HSV

80
Investigation
  • Investigation rarely necessary for Bells palsy
  • Electroneurography
  • Possible investigations
  • CSF examination
  • ESR
  • Blood glucose
  • VDRL test
  • HIV test
  • Brain imaging

81
Management
  • Protect eye during sleep
  • Massage weak muscles
  • Prednisolone 20 mg daily for 10 days
  • Acyclovir not beneficial
  • Acyclovir Prednisolone not beneficial
  • Surgical decompression

82
Complications
  • Oral incompetence
  • Epiphora
  • Facial synkinesis
  • hemifacial spasm
  • Dysgeusia/ageusia
  • Aberrant function of the lacrimal glands
  • crocodile tears
  • shedding tears while eating.
  • Exposure keratopathy

83
Differential diagnosis
  • Möbius syndrome
  • Melkersson Rosenthal syndrome
  • Recurrent facial nerve palsy
  • Facial or labial edema
  • Plication of the tongue
  • Diabetes mellitus, Lyme disease, Sjögren
    syndrome, amyloidosis
  • Ramsay Hunt syndrome
  • Facial nerve palsy
  • Vesicular eruption in the external auditory canal
  • Tumors of parotid gland
  • Facial diplegia, bilateral facial nerve palsy
  • Guillain Barré syndrome
  • Heerfordt syndrome, uveoparotid fever, sarcoidosis

84
Poor prognostic factors
  • Older age
  • Hypertension
  • Impairment of taste
  • Complete facial weakness

85
MYASTHENIA GRAVIS - AN OVERVIEW
  • Dr M.B Fawale

86
INTRODUCTION
  • Myasthenia gravis (MG) is an autoimmune
    neuromuscular disorder xterized by reduced
    skeletal muscle strength with repeated use and
    recovery following a period of rest.
  • The underlying defect is an antibody-mediated
    reduction in the number in Ach nicotinic
    postsynaptic receptors at the myoneural junction.
  • Treatment now available is highly effective
  • Specific cure has remained elusive.

87
PATHOPHYSIOLOGY
  • Autoantibodies develop against ACh nicotinic
    postsynaptic receptors.
  • Reduction of AChRs no. by 3 mechanisms
  • accelerated (2-3fold) turnover of AChRs
  • Mechanical blockade
  • Postsynaptic membrane damage
  • Symptoms when no 30 of normal
  • Pathogenic antibodies - T cell dependent IgG
  • Initiation maintenance of autoimmune response
    not understood.

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PATHOPHYSIOLOGY
  • The thymus appears to play a role
  • Abnormal in 75 of patients.
  • Hyperplasia in 65, thymomas in 10-15.
  • Clinical improvement following thymectomy.
  • Myoid cells may serve as source of autoantigen ?.
  • Virus with a tropism for thymic cells (?)
  • The cholinergic receptors of smooth and cardiac
    muscle have a different antigenicity so, not
    affected.

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EXACERBATING FACTORS
  • Antimicrobials
  • Macrolides
  • Ampicillin
  • Tetracycline
  • Fluoroquinolones
  • Aminoglycosides
  • CQ.
  • Antidysrhythmics
  • BBs, CCBs
  • Quinidine
  • Lidocaine
  • Procainamide trimethaphan
  • Misc.
  • Diphenylhydantoin
  • Lithium, CPZ
  • Muscle relaxants
  • Levothyroxine
  • Anticholinergics
  • ACTH
  • Corticosteroids

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EPIDEMIOLOGY
  • Incidence
  • US - 2/1,000,000, Ibadan 0.07/1000
  • Prevalence 0.5-14.2 cases per 100,000.
  • Sex
  • MF (lt40) 2-31, (gt40) 32
  • Ibadan 12
  • Age
  • 10 lt10yrs
  • Peak F 20-30yrs, M 50-60yrs
  • Race Early onset commonner in Asians.
  • Thymoma 50-60yrs, MgtF

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CLINICAL FEATURES
  • Hallmark progressive weakness with repetitive or
    persistent activity improvement with rest.
  • Onset insidious, infrequently rapid.
  • Presentation and progression vary.
  • Ocular -gt facial -gt bulbar -gt truncal
  • -gt limb muscles.
  • Diaphragm, abdominal intercostal muscles
    external sphincters in advanced cases.

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Clinical Features
  • Weakness demonstrated by sustained activity,
    blinking, upward gaze

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Clinical Features
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CLINICAL FEATURES
  • Ocular palsies and ptosis - initial manifestation
    in 50, later in gt90.
  • Remains ocular in 16. About 87 generalize
    within 13 months.
  • Proximal muscles are far more vulnerable.
  • Usually symmetric, often not.
  • Sensory functions reflexes are unaffected.
  • Little or no wasting.

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CLINICAL FEATURES
  • Demonstrable evidence of coexisting autoimmune
    disorders
  • Hyperthyroidism (10-15)
  • RA, scleroderma, and lupus.
  • Spontaneous remissions are rare. Most, with
    treatment, in the first 3 years.

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Osserman Classification
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INVESTIGATION
  • Tensilon (Edrophonium) test
  • 0.1ml of 10mg/ml, if no response within 1minute,
    0.9ml.
  • IV Atropine to hand
  • ve in ALS, polio, some periph. neuropathies.
  • Ice pack test
  • ve test clear resolution of ptosis in
    2minutes.
  • ve in 80.
  • Repetitive nerve stimulation (RNS)
  • Single-fiber electromyography (SFEMG)

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INVESTIGATION
  • Anti-AChR antibody
  • Anti-striated muscle (anti-SM) Ab
  • Chest x-ray
  • Chest CT scan
  • Thyroid function tests

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TREATMENT
  • Approach is determined by severity, distribution,
    rapidity progression.
  • AChE inhibitors immunomodulating therapies are
    the mainstays of treatment.
  • Mild disease - AChEi initially.
  • Generalized - AChEi immunomodulating therapy.

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AChE INHIBITORS
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TREATMENT
  • Corticosteroids (Prednisone)
  • Sig. improvement/ remission with decreased Ab
    titer, in 1-4 mo.
  • No consensus on dosing schedule.
  • Weakness may worsen in the 1st 3 wks.
  • Trial of withdrawal may be attempted, most
    relapse.
  • Azathioprine
  • For steroid failure or for its steroid-sparing
    effects.
  • Onset of action - 6-12 mo
  • 1 to 2-3mg/kg/d PO

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TREATMENT
  • Azathioprine
  • Reserved for steroid failure or for its
    steroid-sparing effects.
  • Onset of action - 6-12 mo.
  • 1 to 2-3mg/kg/d PO.
  • SE, leukopenia, thrombocytopenia, macrocytic
    anemia hypersensitivity, hepatotoxicity, risk of
    infections neoplasia.

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TREATMENT
  • High-dose IV immunoglobulin
  • Rapid onset of action, short duration of effects.
  • Best used in crisis management
  • 2 g/kg slow IV infusion over 3-5 d.
  • SE Allergy, renal insufficiency, aseptic
    meningitis, TE events flu-like syndrome.
  • Plasma exchange (PE)
  • Removes circulating humoral factors
  • Improvement within days, lasts 6-8 weeks
  • An adjunct to immunomodulatory therapies and for
    crisis management.

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TREATMENT
  • Thymectomy
  • Proposed as first-line therapy in most
    generalized MG.
  • Indications Thymoma, Age 10-55 years with
    generalized MG.
  • May induce remission young patients with a short
    duration of disease, hyperplastic thymus, high
    ab titer.
  • Remission rate increases with time 40-60 7-10
    years after surgery.

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Complications
  • Aspiration pneumonia
  • Respiratory failure
  • Myasthenic crisis
  • Cholinergic crisis
  • Complications of long term immune suppression

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Myasthenic crisis
  • Rapid and severe deterioration of myasthenia.
  • Severe generalized muscle weakness involving
    bulbar respiratory muscles.
  • Respiratory infections, use of contraindicated
    drugs are common ppting factors.
  • Management ICU
  • Intubation mechanical ventilation
  • Plasma exchange or IV immunoglobulin
  • Treat infection
  • Mortality 13

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Cholinergic crisis
  • Results from an excess of cholinesterase
    inhibitors
  • Clinically indistinguishable from weakness due to
    MG
  • CF Miosis and the SLUDGE syndrome
  • Salivation, lacrimation, urinary incontinence,
    diarrhea, GI upset and hypermotility, emesis.
  • Bronchospasm, bronchorrhea, respiratory failure,
    diaphoresis.
  • Tensilon worsens weakness
  • Treatment Anticholinergic Beta-agonist
    bronchodilators

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Lambert Eaton myasthenic syndrome
  • Pathology
  • Antibodies to voltage gated calcium channels on
    the presynaptic membrane
  • There is reduction of quanta release of
    acetylcholine
  • Associations
  • Small cell lung cancers, which express vCa
    channels
  • Non-cancer associated

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Lambert Eaton myasthenic syndrome
  • Muscles affected
  • Trunk, shoulder and pelvic girdles, lower
    extremities
  • Presentation
  • Difficulty in rising from the chair, climbing
    stairs, and walking
  • Ptosis, diplopia, dysarthria, and dysphagia
  • Weakness may improve after few contractions
  • Tendon reflexes are diminished
  • Fasciculations are absent

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Investigations
  • Anti voltage gated calcium channel antibodies
  • May be present in up to 90 of patients
  • Very specific
  • EMG

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Treatment
  • 3,4 Diaminopyridine
  • Blocks presynaptic potassium channels, increases
    opening time of VGCC
  • Non-neoplastic types
  • Intravenous immune globulin
  • Steroids
  • Treatment specific for neoplasms

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MYOPATHIES
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Myopathies - Classification
  • Hereditary
  • Muscular dystrophy
  • Myotonia Channelopathies
  • Congenital myopathies
  • Metabolic myopathies
  • Mitochondrial Myop.
  • Acquired
  • Inflammatory myop.
  • Endocrine myop.
  • Myopathies associated with systemic illnesses
  • Drug induced/toxic myopathies

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Muscular dystrophies
  • Muscular dystrophies are a group of inherited
    primary diseases of muscle, characterized
    pathologically by muscle fiber degeneration and
    clinically by progressive muscle weakness.
  • Pathological, clinical, and genetic criteria have
    been used as the basis for their classification

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Muscular dystrophies - Genetic Classification
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The dystrophin-associated protein complex
LGMD limb-girdle muscular dystrophy CMD
congenital muscular dystrophy MM Miyoshi
myopathy DMD Duchenne muscular dystrophy BMD
Becker muscular dystrophy
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Muscular dystrophies CK Concentration
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Muscles affected in Dystrophinopathies
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Features of Dystrophy
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Duchenne Muscular Dystrophy
  • X-linked disease, affects 1/3,500 live births.
  • Most severe form of the dystrophies
  • Onset in childhood (lt 4 years), noticed when
    child starts to walk clumsiness, falling
    tendencies
  • Proximal muscle weakness
  • Pseudohypertrophy of calf muscles and deltoid
  • Waddling gait, Lordosis, Gowers sign, prominent
    calves
  • Wheel-chair confinement by age 7-12 yrs death in
    late teens from respiratory infection, CCF

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Duchenne muscular dystrophy
Pseudo-hypertrophy of the calf muscles in a
patient with Duchenne muscular dystrophy
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Duchenne muscular dystrophy
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Duchenne Muscular Dystrophy
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Becker Muscular Dystrophy
  • Adult-onset type
  • Benign disease
  • Autosomal recessive
  • Partial deficiency of dystrophin
  • Presents with proximal weakness, myoglobinuria,
    myalgias
  • Elevated CK
  • May be asymptomatic

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Limb-girdle muscular dystrophy
  • Autosomal recessive type
  • Begins in the 3rd decade, severe disability by
    5th decade
  • Winging of scapulae
  • Waddling gait
  • Intellect normal
  • Facial muscles spared
  • Cranial nerves spared
  • Occ. hypertrophy of muscles (30)

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Facioscapulohumeral muscular dystrophy
  • Autosomal dominant
  • Both sexes affected
  • Onset 2nd or 3rd decade insiduous progression
  • Facial weakness with pouting of lips and
    transverse smile
  • No muscle hypertrophy
  • Diagnosis easy with pattern of clinical
    involvement

Facioscapulohumeral muscular dystrophy. Profound
scapular winging with rising of the scapulae
upward and laterally.
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Facioscapulohumeral muscular dystrophy
  • A, Horizontal and widened appearance of the mouth
    with vertical dimpling on either side of the
    mouth. The rest of the face is relatively
    unlined.
  • B, Pouting appearance of the lips when viewed
    from the side.
  • C, Atrophy of the arm due to wasting of the
    biceps and triceps. The deltoid and muscles of
    the forearm are relatively preserved (Popeye
    arm).
  • D, Hypertrophy of the extensor digitorum brevis
    muscle, in spite of marked footdrop, seen as
  • bulging on the lateral aspect of the foot

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Other dystrophinopathies
  • Ocular type
  • Oculo-pharyngeal type
  • Distal type
  • Congenital type (a2 laminin/merosin def.) floppy
    at birth raised CK ch. 6q22-23
  • Fukuyama type Congenital high Ck at birth
    brain atrophy ch 9q31-33 Japanese
  • Emery-Dreifuss MD rare, X-linked early
    contractures, cardiac conduction defects

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Myotonias Channelopathies
  • Channelopathies has come to describe a group of
    disorders caused by mutations in genes coding for
    cell membrane ion channels
  • They could be dystrophic or non-dystrophic
  • Myotonias are xterized by continued active
    contraction of a muscle which persists after
    cessation of voluntary effort or stimulation
    (difficulty in relaxation after sustained
    contraction)
  • The most common myotonic myopathy is myotonic
    muscular dystrophy

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Dystrophia myotonica
  • Complex multi-system disease with variable
    expression
  • Autosomal dominant mode of inheritance
  • Associated with tri-nucleotide CTG repeat
    expansion
  • Variable age of onset
  • Childhood onset (Thomsens disease)
    generalised myotonia weakness floppiness
    mental retardation and characteristic facies
    hatchet jaw, lowset ears
  • Adolescence distal weakness and wasting
  • Older Age cataracts, frontal balding

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Pertinent clinical features in Dystrophia
myotonica
  • Bilateral ptosis
  • Myotonia worse in cold weather
  • Distal wasting usually in the hands
  • Cataracts, Frontal baldness Gonadal atrophy
  • Progressive mental defect personality change
  • Cardiac conduction defects
  • Apathetic appearance
  • Normal CK, Myotonic EMG
  • Treatment with Procainamide, Quinidine,
    Phenytoin, Steroids

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Dystrophia myotonica
Congenital myotonic dystrophy. Facial diplegia,
ptosis, temporal, and masseter muscle wasting and
the characteristic appearance of the mouth (like
an inverted V)
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Dystrophia myotonica
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Myotonias Channelopathies
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Myotonias Channelopathies
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Treatment of muscle diseases
  • Antibiotics
  • Treat or eliminate identified precipitant
  • Treat complications (if any)
  • Steroids (Prednisolone tried in DMD)
  • Cytotoxics where indicated
  • Analgesics
  • Physiotherapy walking aids
  • Genetic counselling
  • Myoblast transfer Dystrophin gene insertion

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Inflammatory myopathies
  • Dermatomyositis (DM), polymyositis(PM), and
    inclusion body myositis(IBM) are the three major
    categories
  • Diagnosis
  • clinical signs/symptoms
  • CPK
  • Serology - antibodies - RF, ANA
  • EMG - myopathic
  • muscle biopsy
  • Treatment
  • steroids or immunosuppressives

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Inflammatory myopathies
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Inflammatory myopathies
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Dermatomyositis
Dermatomyositis. Heliotrope (violaceous)
discoloration around the eyes and periorbital
edema
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Dermatomyositis
Gottron's papules, pathognomonic of
dermatomyositis Round, smooth,
violaceous-to-red, flat-topped papules that occur
over the knuckles and along the sides of the
fingers.
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Dermatomyositis
Violaceous erythema and Gottron's papules
Periungual erythema and telangiectasia
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Dermatomyositis
Violaceous scaling patches on the face and
dorsal interphalangeal joints. The knuckles are
involved they are spared in SLE
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