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Cranial nerves

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Trigeminal nerve

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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

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Human Anatomy, Frolich, Head/Neck IV: Cranial Nerves

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Trigeminal neuralgia

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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.

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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.

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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

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Surgical treatment Percutaneous risotomy (glycerol injection, baloon compression, radiofrequency risotomy) Peripheral blocks, section, avulsion Microsurgery risotomy Gammaknife radiosurgery

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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

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Facial nerve

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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.

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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.

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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

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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

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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)

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Complications Keratitis Emotional/Social Issues Synkinesis

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Ramsay Hunt Syndrome

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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

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Oculomotricity

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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)

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Ocular motricity MuscleInervationPrimary actionSecondary actionOther actions Medial rectusN IIIAdduction-- superior rectusN IIIElevationInternal rotationAdduction inferior rectusN IIIDepressorExternal rotationAdduction inferior obliqueN IIIExternal rotationelevationAbduction Superior obliqueN IVInternal rotationDepressorAbduction lateral rectusN VIAbduction--

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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

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3 rd nerve - Oculomotor nerve

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VI th nerve abducens

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6 th nerve Abducens nerve

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Abducens nerve palsy (left side)

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4 th nerve Trochlear nerve

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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

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trohlear normal Superior oblique muscle palsy

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joint deviation of the eyes and head

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Internuclear palsies

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Miasthenia gravis

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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

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Healthy Neuromuscular Junction

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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

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Spontaneous and Nerve Evoked Endplate Responses

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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

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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

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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

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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

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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

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Repetitive Nerve Stimulation (Supramaximal 2Hz)

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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

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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)

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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)

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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)

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Repetitive Nerve Stimulation (Supramaximal 2Hz)

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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)

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POLYMYOSITIS DERMATOMYOSITIS

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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

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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

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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

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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;

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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

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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

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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

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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

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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

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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

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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

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Differential diagnosis Myasthenia Gravis Electrolyte disturbances Metabolic, endocrine or toxic myopathies Muscular dystrophy Guillain-Barre Syndrome

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Tratament Corticosteroids Good response to treatment if: Clinical picture: proximal or diffuse motor deficit, disease duration

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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

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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