V: Trigeminal (3 nerves in 1!) V1. Ophthalmic Exits with eye
muscle group (superior orbital fissure, through orbit to superior
orbital notch/foramina) Sensory to forehead, nasal cavity V2.
Maxillary Exits foramen rotundum through the wall of maxillary
sinus to inferior orbital foramina) Sensory to cheek, upper lip,
teeth, nasal cavity V3. Mandibular Exits foramen ovale to
mandibular foramen to mental foramen Motor to jaw
muscles--Masseter, temporalis, pterygoids, digastric Sensory to
chin Sensory to tongue
Slide 5
Human Anatomy, Frolich, Head/Neck IV: Cranial Nerves
Slide 6
Trigeminal neuralgia
Slide 7
TRIGEMINAL NEURALGIA (Tic Douloureux) A disorder of the
trigeminal nerve producing bursts of excruciating, lancinating
pain, lasting between seconds and 2 min, along the distribution of
one or more of its sensory divisions, most often the maxillary.
vascular loops compressing the trigeminal nerve root where it
enters the brainstem usually adults trigger point or by activity
(eg, chewing or brushing the teeth). Although each bout of intense
pain is brief, successive bouts may be incapacitating.
Slide 8
TRIGEMINAL NEURALGIA Differential diagnosis Neoplasm Vascular
malformation of the brain stem, Vascular insult, Multiple sclerosis
(especially in a younger patient). Postherpetic pain typical
antecedent rash, scarring, and predilection for the ophthalmic
division. Sjgren's syndrome or RA, (with a sensory deficit that is
often perioral and nasal). Migraine may produce atypical facial
pain, with normal examination results, but the pain is more
prolonged and is burning or throbbing.
Slide 9
Treatment carbamazepine (Tegretol), fenitoin (Dilantin),
oxcarbazepine (Trileptal), gabapentin (Neurontin). Use of Baclofen
(Lioresal) may increase efficiency Neurontin, (gabapentin), Lyrica
(pregabalin) lower rates of adverse effects
Trigeminal paralysis Weakness, hipotonia and atrophies of the
maseter and temporal muscles Jaw deviates towards affected side
upon closure of the mouth, can not perform jaw lateral movements to
the affected side
Slide 12
Facial nerve
Slide 13
Slide 14
Branchial motor (special visceral efferent) Supplies the
muscles of facial expression; posterior belly of digastric muscle;
stylohyoid, and stapedius. Visceral motor (general visceral
efferent) Parasympathetic innervation of the lcrimal,
submandibular, and sublingual glands, as well as mucous membranes
of nasopharynx, hard and soft palate. Special sensory (special
afferent) Taste sensation from the anterior 2/3 of tongue; hard and
soft palates. General sensory (general somatic afferent) General
sensation from the skin of the concha of the auricle and from a
small area behind the ear.
Slide 15
Bell's Palsy Unilateral facial paralysis of sudden onset and
unknown cause. swelling of the nerve due to immune or viral
disease, with ischemia and compression of the facial nerve in its
course through the temporal bone. Pain behind the ear may precede
facial weakness. Weakness develops within hours, sometimes to
complete paralysis. The patient may complain of a numb or heavy
feeling in the face, but no sensory loss is demonstrable. A
proximal lesion may affect salivation, taste, and lacrimation and
may cause hyperacusis.
Slide 16
Differential Diagnosis Disorders of the facial nerve or its
nucleus, chiefly geniculate herpes (Ramsay Hunt's syndrome), Middle
ear or mastoid infections, Sarcoidosis, Lyme disease, Petrous bone
fractures, Carcinomatous or leukemic nerve invasion, Chronic
meningeal infections, and Cerebellopontine angle or glomus jugulare
tumors. Temporal bone fracture
Slide 17
Slide 18
Slide 19
Bells Palsy Treatment Oral antivirals - Acyclovir - 10mg/kg
(500mg) q8hrs x 7 days Corticosteroid Prednisone taper 1mg / kg /
day for 10 days methylprednisolone Eye protection - lacrilube
Follow progression with serial exams Facial nerve decompression
Performed before irreversible injury to the endoneural tubules
occurs (two weeks), will allow for axonal regeneration to
occur
Slide 20
What if the facial paralysis doesnt resolve? End-to-End
Anastomosis Cable Nerve Graft Hypoglossa-Facial Nerve Anastomosis
(Crossover or Jump Graft) Muscle transposition (Gracilis) Static
Suspension (Gortex, Threads)
Central vs peripheral paralysis Weakness of the entire half of
the face distinguishes Bell's palsy from supranuclear lesions (eg,
stroke, cerebral tumor), in which the weakness is partial,
affecting the frontalis and orbicularis oculi less than the muscles
in the lower part of the face
Slide 24
Oculomotricity
Slide 25
Centre for saccadic (fast) voluntary or reflex movements.
Activation leads to fast deviation of eyes towards opposite side
III rd nerve nucleus Medial longitudinal bundle Reticular
paramedian pontine formation centre for lateral
Fronto-mezencephalic pathway Occipito-mesencephalic pathway Centre
for slow following motions. Activation leads to slow deviation of
eyes (both pathways end in the oculomotor nerves nuclei)
3 rd nerve - Oculomotor nerve Somatic fibers: 4 out of the 6
extraoculary muscles and also the elevator of the upper lid Control
of the eye movements during following or fixation movements
Visceral fibers: parasympathetic fibers for the pupilar constrictor
and ciliary muscles Involved in the accomodation pupilary
reflexes
Slide 28
3 rd nerve - Oculomotor nerve
Slide 29
Slide 30
Slide 31
VI th nerve abducens
Slide 32
6 th nerve Abducens nerve
Slide 33
Abducens nerve palsy (left side)
Slide 34
4 th nerve Trochlear nerve
Slide 35
Trochlear nerve Contraction of the superior oblique muscle
generates depression, internal rotation and abduction of the eye
Lesions of the 4 th nervegenerate External rotation (unbalanced
action of inferior oblique muscle) Diplopia (vertical) Problems
with looking down, especially for the eye that looks internally
problems with descending stairs Compensatory rotation of the head
Due to its long way around the brainstem, the 4 th nerve is prone
to lesions in head trauma Special features: Trasaturi speciale:
Theonly cranial nerve that emerges on the posterior side of the
midbrain All fibers from the lower motor neuron cross It has the
longest intracranian passage Contains the least axons compared to
the other cranian nerves
Slide 36
trohlear normal Superior oblique muscle palsy
Slide 37
joint deviation of the eyes and head
Slide 38
Internuclear palsies
Slide 39
Miasthenia gravis
Slide 40
The Anatomy of the Neuromuscular Junction Motor neurone
terminates as a bouton or pre- synaptic nerve terminal separated
from the muscle by a thin synaptic cleft (Motor endplate) The blood
nerve barrier is relatively deficient at the NMJ Nerve and muscle
are kept in close proximity by bridging protein (laminin), with
release zones and the crests of post synaptic folds aligned The
skeletal neuromuscular junction is the most studied and best
understood synapse
Slide 41
Healthy Neuromuscular Junction
Slide 42
The Physiology of Neuromuscular transmission Neuronal Action
potential invades the pre- synaptic nerve terminal Depolarisation
triggers opening of VGCCs Calcium influx triggers quantal release
of ACh ACh binds to post synaptic nAChRs Ca and Na ions influx
through nAChR triggering muscle membrane depolarisation via VGSCs-
CMAP and muscle contraction
Slide 43
Spontaneous and Nerve Evoked Endplate Responses
Slide 44
Myasthenia Gravis (MG) MG is the most common disorder of
neuromuscular transmission Incidence 2-6 per 106, prevalence 40 per
106 population MG is an acquired autoimmune disease characterised
by the formation of anti- nAChR antibodies MG is common in young
women, and older men MG is characterized by fluctuating and
fatigable weakness Weakness may be limited to a few muscles, such
as the extraocular muscles, bulbar, limb or be generalised in
fashion As the weakness is often worse with activity and improved
by rest, it is often worse in the evening
Slide 45
Myasthenia Gravis (MG) Ocular features: ptosis, diplopia,
ophthalmoplegia Facial weakness esp ob oculi and oris (snarl)
Bulbar weakness: nasal speech, reduced gag, swallowing problems,
aspiration (silent), weak neck (dropped) Limb weakness: proximal,
fatiguable Reflexes: normal Respiratory weakness: diaphragm and
intercostal Fenomenul de oboseal (ptoz) n MG
Slide 46
Myasthenia Gravis (MG) MG is a defect of neuromuscular
transmission with reduced efficacy of Acetyl Choline at the post
synaptic motor endplate due to pathogenic antibodies which Block
the nAChR, Down regulate the nAChR & cause complement dependent
destruction of the motor endplate
Slide 47
Myasthenia Gravis (MG) The immunopathogenesis of MG is unclear
but involves Genetic factors (HLA B8) Thymus Vast majority of young
onset cases are autoimmune and associated with thymic hyperplasia
Around 10% of patients with MG, often older patients) have an
associated thymic tumour (oft striated muscle Abs) Seronegative
(10% gen, 50% OMG) Neonatal MG
Slide 48
Myasthenia Gravis (MG) Diagnosis Typical clinical picture
Detection of anti-AChR antibodies in serum (90%) Positive Tensilon
test (atropine) Repeptitive nerve stimulation at low frequency
leads to a decrement in compound muscle action potential amplitude
Tensilon test before and after Single fiber EMG normal Single fiber
EMG increased jitter
Slide 49
Repetitive Nerve Stimulation (Supramaximal 2Hz)
Slide 50
Myasthenia Gravis (MG) Treatment Symptomatic (pyridostigmine
oft with probatheline) Thymectomy Hyperplasia (trans-sternal
approach), Thymoma (locally invasive) Immunotherapy steroids, and
other agents including Azathioprine plasma exchange, IVIG
Slide 51
Lambert Eaton Myasthenic syndrome (LEMS) A defect of
neuromuscular transmission with reduced quantal release of Acetyl
Choline from the presynaptic nerve terminal Pathogenic antibodies
directed against voltage gated calcium channels (VGCCS) expressed
at the NMJ and autonomic ganglia 2/3 patients with LEMS have
cancer, most commonly Small cell lung Ca (express VGCCs)
Slide 52
Lambert Eaton Myasthenic syndrome (LEMS) Clinical features Dry
mouth Fatigable weakness of proximal muscles (like MG) Wasting of
proximal muscles (X MG) Depressed reflexes (X MG) Ocular and bulbar
weakness rare (X MG)
Slide 53
Lambert Eaton Myasthenic syndrome (LEMS) Diagnosis Typical
clinical picture Detection of anti-VGCC antibodies in serum
Positive Tensilon test (like MG) Repeptitive nerve stimulation at
low frequency leads to a decrement in compound muscle action
potential amplitude (like MG) Repeptitive nerve stimulation at high
frequency leads to a increment in compound muscle action potential
amplitude (X MG)
Slide 54
Repetitive Nerve Stimulation (Supramaximal 2Hz)
Slide 55
Lambert Eaton Myasthenic syndrome (LEMS) Treatment Treating the
underlying lung tumour improves LEMS Treatment for LEMS per se
Symptomatic (mestinon, 3-4 DAP) Immunotherapy (steroids, plasma
exchange, IVIG)
Slide 56
POLYMYOSITIS DERMATOMYOSITIS
Slide 57
CLASSIFICATION OF POLYMYOSITIS - DERMATOMYOSITIS Group I:
Primary Idiopathic PM Group II: Primary Idiopathic DM Group III: DM
or PM associated with neoplasia Group IV: Childhood DM or PM
associated with vasculitis Group V: PM or DM with associated with
collagen diseases
Slide 58
POLYMYOSITIS - DERMATOMYOSITIS Onset age: Usually > 20 years
Progression: weeks-months Possibly preceded by upper tract
infection Other possible trigger factors: Anti hepatitis B
vaccination Growth hormone administration Drugs: penicilamine Viral
infections: Coxsackie B; Parvovirus; Echovirus HLA Class II:
antigens DQ1*0501 (88%) For DM: DMA*0103 si DMB*0102
Slide 59
Clinical Picture Muscle weakness Proximal > Distal Symmetric
Frequently starts at lower limbs Selective regions of weakness:
eophagus (dysphagia); Posterior neck; Quadriceps Usually does not
affect oculomotor muscles Amiotrophies occur late in the evolution
Reflexes usually normal
Slide 60
Motor deficit Proximal: most frequently in PM and DM Distal:
inclusion body myositis Lack of simmetry: inclusion body myositis
cvadriceps: inclusion body myositis; PM with mitochondrial diseases
Extraocular muscles: extraoculary myositis Swallowing : inclusion
myositis, granulomatous myositis, scleroderma associated myositis
Episodic: episodic miopathy with pipestem capilaries Acute:
infectious;
Slide 61
Skin lesions (DM) Heliotrope rash - reddish violaceous eruption
on upper eyelids +/- oedema Diffuse/localised erythema over chest,
neck, or over forehead, chin, malar area Gottrons sign - symmetric
violaceous erythematous eruption over knuckles Necrosis Gottron
sign
Slide 62
Pain 30%; Especially with associated connective tissue disease
Rule out: Polymyalgia; Arthritis; Fasciitis; Rhabdomyolysis Muscle
pain Associated with contraction, muscle mass compression or
spontaneous pain Joint pain Arthrites or nondestructive arthralgia
Anti-Jo1 or AntiARNt synthethasys antibody syndromes
Slide 63
Associated disorders Cardiac: Arhythmias; Inflammatory
cardiomyopathy Pulmonary: Respiratory muscle weakess; Interstitial
lung disease Esophageal paresis: Upper 1/3 with muscle weakness,
Lower 2/3 with scleroderma Abdominal pain: GIT mucosal involvement
Marked by ulceration, hemorrhages & perforation Due to
associated vasculopathy Malignancy: Mild increased risk
Autoimmune:Lupus, Sjoegren's, Anti-phospholipid antibodies &
syndrome: 5% to 8% Thyrotoxicosis: Rare High CK: CK in hyperthyroid
is usually low May resolve with anti-thyroid medication alone
Calcinosis (formation of calcium deposits in any soft tissue) in
1/3 of cases
Slide 64
Clinical forms (evolutive) Acute: Important motor deficit, fast
prograssion, muscle pain, fever, inflamation signs, myoglobinuria
Possible death within weeks due to reapiratory destress, heart
failure, kidney feilure Subacute Cronic Focal forms rare; sometimes
evoluate towards difuse type
Slide 65
Laboratory Serum CK: High (3 to 30 times normal); elevated LDH,
aldolase, AST, ALT General inflamation signs (CRP) EMG: Irritative
myopathy Small amplitude, brief, polyphasic motor units
Fibrillations; Positive sharp waves spontaneous high frequency
discharges Antibodies: Disease specific & non-specific
Slide 66
EMG aspects Long duration positive sharp waves : Initial
positive deflaction followed by a negative component Fibrilation:
Short duration potentials (arrows) with positive and then negative
component Polyphasic action potentials with small amplitude, short
duration
Slide 67
Muscle biopsy Myopathic Variation in size of muscle fibers
Necrosis + phagocytosis & regeneration of muscle fibers Mild,
patchy increase in endomysial connective tissue Inflammation
Endomysial & perivascular inflammatory (mononuclear) cells
Macrophages & CD8+ T-cells Focal invasion of non-necrotic
muscle fibers Muscle fiber necrosis MAC (complement) deposits at
the surface of the muscle fibers
Tratament Corticosteroids Good response to treatment if:
Clinical picture: proximal or diffuse motor deficit, disease
duration
Slide 70
TREATMENT Cytotoxic agents introduced if severe disease,
relapsing disease, inadequate steroid response or steroid induced
cxs. AZA or methotrexate used with steroids Cyclosporin,
cyclophosphamide, tacrolimus and antiTNF are alternatives.
Intravenous immunoglobulin successful Child DM, esophageal
dysfunction 1gram/kg/day
Slide 71
Secondary myositis Malignancy lung cancer, gastric, prostate,
mamary, ovary Surgical intervention does not always lead to a
favourable evolution Drug induced:D-penicilamine; Procainamide,
Hidralazine (Lupus miozitis); Interferon-; Fenitoin (inflamatory
myopaty with fever, rash, limphadenopaty and eosinophyilia);
Possibly related with myositis: Peniciline; Ypeca; Sulfonamide;
Levodopa; Cimetidine; Leuprolide; Propilthiouracil; Carbimazole
Graft versus host reaction