PERIPHERAL NERVES, MUSCLE AND EYE
Transcript of PERIPHERAL NERVES, MUSCLE AND EYE
PERIPHERAL NERVES, MUSCLE AND EYE
PERIPHERAL NEUROPATHIES• GUILLAIN-BARRE SYNDROME
• RAPIDLY PROGRESSIVE ACUTE DEMYELINATING DISORDER AFFECTING MOTOR AXONS,
RESULTING IN ASCENDING WEAKNESS THAT CAN LEAD TO DEATH FROM FAILURE OF
RESPIRATORY MUSCLES WITHIN DAYS OF ONSET OF SYMPTOMS
• TRIGGERED BY AN INFECTION OR VACCINATION THAT BREAKS DOWN SELF-TOLERANCE
LEADING TO AN AUTOIMMUNE RESPONSE
• CHRONIC INFLAMMATORY DEMYELINATING POLYNEUROPATHY (CIDP)
• CHARACTERIZED BY SYMMETRICAL MIXED SENSORIMOTOR POLYNEUROPATHY THAT
PERSISTS FOR 2 MONTHS OR MORE (RELAPSING/REMITTING OR PROGRESSIVE COURSE)
• BOTH MOTOR AND SENSORY ABNORMALITIES ARE COMMON
• IMMUNE MEDIATED LIKE GUILLAIN-BARRE SYNDROME
• PERIPHERAL NERVES SHOW SEGMENTS OF DEMYELINATION AND REMYELINATION; CAN
ALSO SEE CONCENTRIC ARRANGEMENT OF MULTIPLE SCHWANN CELLS AROUND
INDIVIDUAL AXONS PRODUCING ONION BULB-LIKE STRUCTURES
• DIABETIC PERIPHERAL NEUROPATHY
• THE MOST COMMON CAUSE OF PERIPHERAL NEUROPATHY SEEN WITH LONGSTANDING
DISEASE
• CONSTELLATION OF FINDINGS INCLUDE AUTONOMIC NEUROPATHY, LUMBOSACRAL
RADICULOPATHY AND DISTAL SYMMETRIC SENSORIMOTOR POLYNEUROPATHY
NEUROMUSCULAR JUNCTION DISORDERS• MYASTHENIA GRAVIS
• AUTOIMMUNE DISEASE WITH FLUCTUATING MUSCLE WEAKNESS THAT IS CAUSED BY
AUTOANTIBODIES THAT TARGET THE NEUROMUSCULAR JUNCTION
• MOST COMMON ANTIGENIC TARGET IS THE POSTSYNAPTIC ACETYLCHOLINE RECEPTOR
• SHOW A BIMODAL AGE DISTRIBUTION WITH DISTINCTIVE CLINICAL FEATURES:
• EARLY ONSET – MORE COMMON IN FEMALES AND ASSOCIATED WITH THYMIC
HYPERPLASIA
• LATE ONSET – EQUAL GENDER DISTRIBUTION AND ASSOCIATED WITH THYMOMA
• DISEASE MANIFESTS WITH PTOSIS AND/OR DIPLOPIA AND REPETITIVE FIRING OF MUSCLES
MAKES THE WEAKNESS MORE SEVERE
• EFFECTIVE TREATMENTS INCLUDE CHOLINESTERASE INHIBITORS, IMMUNOSUPPRESSION,
PLASMAPHERESIS AND THYMECTOMY
• LAMBERT-EATON SYNDROME
• CAUSED BY AUTOANTIBODIES THAT INHIBIT THE FUNCTION OF PRESYNAPTIC CALCIUM
CHANNELS THEREBY REDUCING THE RELEASE OF ACETYLCHOLINE INTO THE SYNAPTIC CLEFT
• PATIENTS EXPERIENCE IMPROVEMENT IN WEAKNESS WITH REPETITIVE STIMULATION
• OFTEN ARISES AS A PARANEOPLASTIC DISORDER, PARTICULARLY SMALL CELL CARCINOMA
• CHOLINESTERASE INHIBITORS ARE NOT EFFECTIVE TREATMENT
PERIPHERAL NERVE SHEATH TUMORS• SCHWANNOMAS
• BENIGN ENCAPSULATED TUMORS THAT MAY OCCUR IN SOFT TISSUES, INTERNAL
ORGANS OR SPINAL NERVE ROOTS
• MOST COMMONLY AFFECTED IS THE 8TH CRANIAL NERVE
• MOST ARE SPORADIC BUT 10% ARE ASSOCIATED WITH NEUROFIBROMATOSIS
TYPE 2 (NF2)
• NF2 PATIENTS ARE AT RISK OF DEVELOPING MULTIPLE SCHWANNOMAS (BILATERAL
VESTIBULAR SCHWANNOMA), MENINGIOMAS AND EPENDYMOMAS; DO NOT DEVELOP
NEUROFIBROMAS
• DUE TO LOSS OF FUNCTION MUTATION IN THE MERLIN GENE ON CHROMOSOME 22
• MORPHOLOGICALLY, TUMORS ARE COMPOSED OF SCHWANN CELLS AND SHOW
AN ADMIXTURE OF DENSE AND LOOSE AREAS REFERRED TO AS ANTONI A AND
ANTONI B
• ANTONI A – COMPOSED OF BLAND SPINDLE CELLS WITH BUCKLED NUCLEI ARRANGED
INTO INTERSECTING FASCICLES; THESE CELLS OFTEN ALIGN TO PRODUCE NUCLEAR
PALISADING RESULTING IN ALTERNATING BANDS OF NUCLEAR AND ANUCLEAR AREAS
(VEROCAY BODIES)
• ANTONI B– SPINDLE CELLS ARE SPREAD APART BY A PROMINENT MYXOID
EXTRACELLULAR MATRIX; THICK-WALLED HYALINIZED VESSELS OFTEN ARE PRESENT
SCHWANNOMA
PERIPHERAL NERVE SHEATH TUMORS
• NEUROFIBROMAS
• BENIGN TUMORS GROUPED INTO THREE SUBTYPES:
• LOCALIZED CUTANEOUS NEUROFIBROMAS – ARISE AS SUPERFICIAL NODULAR OR POLYPOID TUMORS;
OCCUR AS EITHER SOLITARY SPORADIC LESIONS OR AS MULTIPLE LESIONS IN THE SETTING OF
NEUROFIBROMATOSIS TYPE I (NF1)
• PLEXIFORM NEUROFIBROMAS – GROW DIFFUSELY WITHIN THE CONFINES OF A NERVE OR NERVE PLEXUS
AND VIRTUALLY PATHOGNOMONIC FOR NF1; HARBOR A SMALL RISK OF MALIGNANT TRANSFORMATION
(MALIGNANT PERIPHERAL NERVE SHEATH TUMOR)
• DIFFUSE NEUROFIBROMAS – INFILTRATING PROLIFERATIONS THAT CAN TAKE THE FORM OF LARGE,
DISFIGURING SUBCUTANEOUS MASSES (OFTEN ASSOCIATED WITH NF1)
• NEUROFIBROMATOSIS TYPE 1 (NF1)
• AUTOSOMAL DOMINANT DISORDER CAUSED BY MUTATIONS IN THE TUMOR SUPPRESSOR NEUROFIBROMIN
ENCODED ON THE LONG ARM OF CHROMOSOME 17 (NEGATIVE REGULATOR OF RAS)
• CLINICAL FINDINGS INCLUDE NEUROFIBROMAS, MALIGNANT PERIPHERAL NERVE SHEATH TUMORS, OPTIC
GLIOMAS, PIGMENTED NODULES OF THE IRIS (LISCH NODULES) AND PIGMENTED SKIN LESIONS
• MORPHOLOGY:
• NOT ENCAPSULATED; THEY MAY APPEAR CIRCUMSCRIBED OR MAY EXHIBIT DIFFUSELY INFILTRATIVE
GROWTH
• THE NEOPLASTIC SCHWANN CELLS ARE ADMIXED WITH OTHER CELL TYPES INCLUDING MAST CELLS,
FIBROBLAST- LIKE CELLS AND PERINEURAL-LIKE CELLS
• BACKGROUND STROMA OFTEN CONTAINS LOOSE WAVY COLLAGEN BUNDLES (SHAVED CARROT
APPEARANCE) BUT CAN ALSO BY MYXOID OR CONTAIN DENSE COLLAGEN
NEUROFIBROMA
DUCHENNE AND BECKER MUSCULAR DYSTROPHY
• X-LINKED DISEASES CAUSED BY MUTATIONS THAT DISRUPT THE FUNCTION OF THE LARGE
STRUCTURAL PROTEIN DYSTROPHIN
• DUCHENNE MUSCULAR DYSTROPHY (DMD)
• BECOMES EVIDENT EARLY IN CHILDHOOD AND FOLLOWS AN INVARIABLY FATAL COURSE
• OFTEN HAVE DELETIONS OR FRAMESHIFT MUTATIONS OF DYSTROPHIN OFTEN LEADING TO
COMPLETE ABSENCE OF DYSTROPHIN ON MUSCLE BIOPSY
• CLINICAL FEATURES:
• WEAKNESS BEGINS IN THE PELVIC GIRDLE AND THEN IN THE SHOULDER GIRDLE
• CALF PSEUDOHYPERTROPHY IS A COMMON EARLY FINDING
• CARDIAC MUSCLE DAMAGE AND FIBROSIS MAY LEAD TO HEART FAILURE AND ARRHYTHMIAS
• HIGH SERUM CREATINE KINASE LEVELS ARE PRESENT AT BIRTH AND PERSIST THROUGH THE 1ST DECADE OF LIFE
• DEATH RESULTS FROM RESPIRATORY INSUFFICIENCY, PNEUMONIA AND CARDIAC DECOMPENSATION
• BECKER MUSCULAR DYSTROPHY (BMD)
• LESS COMMON AND LESS SEVERE THAN DMD (CAN HAVE A NEARLY NORMAL LIFE SPAN)
• OFTEN HAVE POINT MUTATIONS OF DYSTROPHIN OFTEN LEADING RESIDUAL BUT DEFECTIVE FORMS
OF DYSTROPHIN
• MORPHOLOGY:
• ALTERATIONS IN DMD AND BMD ARE SIMILAR BUT MILDER IN BMD
• ONGOING MYOFIBER NECROSIS AND REGENERATION
• PROGRESSIVE REPLACEMENT OF MUSCLE TISSUE BY FIBROSIS AND FAT
• MUSCLES TYPICALLY SHOW MARKED VARIATION IN MYOFIBER SIZE AND ABNORMAL INTERNALLY
PLACED NUCLEI
DUCHENNE MUSCULAR DYSTROPHY
OTHER INHERITED DISORDERS OF SKELETAL MUSCLE• MYOTONIC DYSTROPHY
• MYOTONIA, THE SUSTAINED INVOLUNTARY CONTRACTION OF A GROUP OF MUSCLES, IS THE
CARDINAL NEUROMUSCULAR SYMPTOM
• A NUCLEOTIDE REPEAT EXPANSION DISEASE (CTG REPEATS) INVOLVING MUTATIONS IN THE GENE
THAT ENCODES THE DYSTROPHIA MYOTONICAPROTEIN KINASE (DMPK)
• MALIGNANT HYPERTHERMIA
• AN ION CHANNEL MYOPATHY CHARACTERIZED BY TACHYCARDIA, TACHYPNEA, MUSCLE SPASMS
AND HYPERPYREXIA
• TRIGGERED WHEN PATIENTS CARRYING MUTATIONS IN THE RYANODINE RECEPTOR RYR1, A
CALCIUM EFFLUX CHANNEL, RECEIVE HALOGENATED ANESTHETIC AGENTS OR SUCCINYLCHOLINE
DURING SURGERY
• ON EXPOSURE TO ANESTHETIC, THE MUTATED RECEPTOR LEADS TO INCREASED EFFLUX OF CALCIUM FROM
THE SARCOPLASMIC RETICULUM, PRODUCING TETANY AND EXCESSIVE HEAT PRODUCTION
• MITOCHONDRIAL MYOPATHIES
• STEM FROM MUTATIONS IN EITHER MITOCHONDRIAL OR NUCLEAR GENOMES BECAUSE BOTH
ENCODE PROTEINS AND RNA THAT ARE CRITICAL FOR MITOCHONDRIAL FUNCTION
• MANIFEST IN EARLY ADULTHOOD WITH PROXIMAL MUSCLE WEAKNESS AND SEVERE INVOLVEMENT
OF THE OCULAR MUSCULATURE
• SOME ARE ASSOCIATED WITH NORMAL MUSCLE MORPHOLOGY; OTHERS SHOW AGGREGATES OF
ABNORMAL MITOCHONDRIA WHICH IMPART A BLOTCHY RED APPEARANCE IN SPECIAL STAINS
(RAGGED RED FIBERS)
INFLAMMATORY MYOPATHIES
• POLYMYOSITIS
• AUTOIMMUNE DISORDER ASSOCIATED WITH INCREASED EXPRESSION OF MHC CLASS I MOLECULES ON
MYOFIBERS
• CHARACTERIZED BY ENDOMYSIAL INFLAMMATORY INFILTRATES CONTAINING CD8+ CYTOTOXIC T-
CELLS AND MYOFIBER NECROSIS
• TREATED WITH CORTICOSTEROIDS OR OTHER IMMUNOSUPPRESSIVE AGENTS
• DERMATOMYOSITIS
• MOST COMMON INFLAMMATORY MYOPATHY IN CHILDREN
• OFTEN MANIFESTS AS A PARANEOPLASTIC DISORDER IN ADULTS
• ASSOCIATED WITH SKIN MANIFESTATIONS AND SYSTEMIC MANIFESTATIONS
• MORPHOLOGICALLY, IT IS ASSOCIATED WITH PERIVASCULAR MONONUCLEAR CELL INFILTRATES WITH
PLASMA CELLS, DROPOUT OF CAPILLARIES, TUBULORETICULAR INCLUSIONS IN ENDOTHELIAL CELLS AND
MYOFIBER DAMAGE IN A PARASEPTAL OR PERIFASCICULAR PATTERN
• RELATIVELY SPECIFIC ANTIBODIES INCLUDE THOSE AGAINST MI-2, P155 AND P140
• INCLUSION BODY MYOSITIS
• MOST COMMON INFLAMMATORY MYOPATHY IN PATIENTS OLDER THAN 60 YEARS OF AGE
• MORPHOLOGIC HALLMARK IS THE PRESENCE OF RIMMED VACUOLES THAT CONTAIN AGGREGATES OF
THE SAME PROTEINS THAT ACCUMULATE IN THE BRAINS OF PATIENTS WITH NEURODEGENERATIVE
DISEASES
• FOLLOWS A CHRONIC PROGRESSIVE COURSE AND GENERALLY DOES NOT RESPOND WELL TO
IMMUNOSUPPRESSIVE AGENTS
INFLAMMATORY MYOPATHIES
CORNEAL DEGENERATIONS AND DYSTROPHIES• BAND KERATOPATHIES
• SERVE AS EXAMPLES OF CORNEAL DEGENERATIONS
• CALCIFIC BAND KERATOPATHY – CHARACTERIZED BY DEPOSITION OF CALCIUM IN BOWMAN’S LAYER
• MAY COMPLICATE CHRONIC UVEITIS ESPECIALLY IN PATIENTS WITH CHRONIC JUVENILE RHEUMATOID ARTHRITIS
• ACTINIC BAND KERATOPATHY – EXTENSIVE SOLAR ELASTOSIS DEVELOPS IN THE SUPERFICIAL LAYERS OF THE CORNEAL
COLLAGEN
• DEVELOPS IN PATIENTS WHO ARE EXPOSED CLINICALLY TO HIGH LEVELS OF ULTRAVIOLET LIGHT
• THE SUN-DAMAGED COLLAGEN APPEARS YELLOW (OIL-DROPLET KERATOPATHY)
• KERATOCONUS
• CHARACTERIZED BY PROGRESSIVE THINNING AND ECTASIA OF THE CORNEA WITHOUT EVIDENCE OF INFLAMMATION OR
VASCULARIZATION GIVING THE CORNEA A CONICAL SHAPE
• IS TYPICALLY BILATERAL AND IS SOMETIMES ASSOCIATED WITH DOWN SYNDROME, MARFAN SYNDROME AND ATOPIC
DISORDERS
• MORPHOLOGY:
• THINNING OF THE CORNEA WITH BREAKS IN BOWMAN’S LAYER ARE CHARACTERISTIC
• CORNEAL HYDROPS – RUPTURE OF DESCEMET’S MEMBRANE WITH AQUEOUS HUMOR GAINING ACCESS TO THE CORNEAL
STROMA CAUSING SUDDEN LOSS OF VISION
• FUCHS ENDOTHELIAL DYSTROPHY
• EARLY, ENDOTHELIAL CELLS PRODUCE DROPLIKE DEPOSITS OF ABNORMAL BASEMENT MEMBRANE MATERIAL (GUTTATA)
• WITH PROGRESSION, THERE IS A DECREASE IN THE TOTAL NUMBER OF ENDOTHELIAL CELLS
• CONSEQUENTLY, THE STROMA BECOMES EDEMATOUS AND THICKENS, ACQUIRES A GROUND GLASS APPEARANCE
CLINICALLY AND LEADS TO BLURRY VISION AND VISION LOSS
• WITH INCREASING STROMAL EDEMA, THE EPITHELIUM UNDERGOES HYDROPIC CHANGE WITH DETACHMENT OF THE
EPITHELIUM FROM BOWMAN’S LAYER PRODUCING EPITHELIAL BULLAE
KERATOCONUS
FUCHS DYSTROPHY
THE ANTERIOR SEGMENT AND GLAUCOMA
• THE ANTERIOR SEGMENT CONSISTS OF THE CORNEA, ANTERIOR CHAMBER, POSTERIOR
CHAMBER, IRIS AND LENS
• GLAUCOMA – CHARACTERIZED BY DISTINCTIVE CHANGES IN THE VISUAL FIELD AND IN THE CUP
OF THE OPTIC NERVE, AND ARE OFTEN ASSOCIATED WITH ELEVATED INTRAOCULAR PRESSURE;
CLASSIFIED INTO TWO MAJOR CATEGORIES:
• OPEN ANGLE GLAUCOMA – THE AQUEOUS HUMOR HAS COMPLETE PHYSICAL ACCESS TO THE
TRABECULAR MESHWORK AND THE ELEVATION IN IN INTRAOCULAR PRESSURE RESULTS FROM AN
INCREASED RESISTANCE TO AQUEOUS OUTFLOW IN THE OPEN ANGLE
• PRIMARY OPEN ANGLE GLAUCOMA – MOST COMMON FORM OF GLAUCOMA; MUTATIONS IN THE
GLC1A GENE ENCODING MYOCILIN COMMONLY IMPLICATED
• SECONDARY OPEN ANGLE GLAUCOMA – MULTIPLE CAUSES INCLUDING SENESCENT RED BLOOD CELLS
AFTER TRAUMA (GHOST CELL GLAUCOMA), IRIS PIGMENT EPITHELIAL GRANULES (PIGMENTARY
GLAUCOMA) AND NECROTIC TUMORS (MELANOMALYTIC GLAUCOMA)
• ANGLE CLOSURE GLAUCOMA – THE PERIPHERAL ZONE OF THE IRIS ADHERES TO THE TRABECULAR
MESHWORK AND PHYSICALLY IMPEDES THE EGRESS OF AQUEOUS HUMOR FROM THE EYE
• PRIMARY ANGLE CLOSURE GLAUCOMA – TYPICALLY DEVELOPS IN EYES WITH SHALLOW ANTERIOR
CHAMBERS, OFTEN FOUND IN PATIENTS WITH HYPEROPIA
• SECONDARY ANGLE CLOSURE GLAUCOMA – MULTIPLE CAUSES INCLUDING NEOVASCULAR
GLAUCOMA AND IRIDOCORNEAL ENDOTHELIAL SYNDROME
THE ANTERIOR SEGMENT AND GLAUCOMA
THE RETINA
• RETINAL DETACHMENT – SEPARATION OF THE NEUROSENSORY RETINA FROM THE RETINAL
PIGMENT EPITHELIUM
• RHEGMATOGENOUS RETINAL DETACHMENT – ASSOCIATED WITH A FULL-THICKNESS RETINAL
DEFECT
• NON-RHEGMATOGENOUS RETINAL DETACHMENT – NOT ASSOCIATED WITH A RETINAL BREAK
OR TEAR WHERE THE SUBRETINAL SPACE IS FILLED WITH PROTEIN-RICH EXUDATE
• RETINAL VASCULAR DISEASE
• MALIGNANT HYPERTENSION – THICKENING AND DAMAGE TO CHOROIDAL VESSELS MAY
PRODUCE FOCAL CHOROIDAL INFARCTS SEEN CLINICALLY AS ELSCHNIG’S SPOTS
• CLINICALLY, THE VESSELS APPEAR NARROWED AND THE COLOR OF THE BLOOD COLUMN MAY
CHANGE FROM BRIGHT RED TO COPPER OR SILVER DEPENDING ON THE DEGREE OF VASCULAR
WALL THICKNESS
• DIABETES MELLITUS – ASSOCIATED WITH RETINAL MICROANGIOPATHY WHICH IS CLASSIFIED
INTO:
• BACKGROUND (PREPROLIFERATIVE) DIABETIC RETINOPATHY – CONSISTS OF BASEMENT
MEMBRANE THICKENING OF RETINAL BLOOD VESSELS, MICROANEURYSMS, MACULAR EDEMA AND
HEMORRHAGIC EXUDATES
• PROLIFERATIVE DIABETIC RETINOPATHY – THE APPEARANCE OF NEW VESSELS THAT SPROUT FROM
EXISTING VESSELS (NEOVASCULAR MEMBRANE)
AGE-RELATED MACULAR DEGENERATION (ARMD)
• MOST COMMON CAUSE OF IRREVERSIBLE VISUAL MORBIDITY IN THE UNITED
STATES
• ETIOLOGY OF THE CONDITION IS UNCLEAR BUT SMOKING, NUTRITIONAL
FACTORS, ATHEROSCLEROSIS AND HYPERTENSION HAVE ALL BEEN IMPLICATED
• CHARACTERIZED CLINICALLY BY LOSS OF VISION IN THE CENTER OF THE VISUAL
FIELD
• ATROPHIC (DRY) ARMD - DIFFUSE OR DISCRETE DEPOSITS IN BRUCH’S MEMBRANE
AND GEOGRAPHIC ATROPHY OF THE RETINAL PIGMENT EPITHELIUM
• EXUDATIVE (WET) ARMD – CHARACTERIZED BY THE DEVELOPMENT OF CHOROIDAL
NEOVASCULAR MEMBRANES (ASSOCIATED WITH MORE SEVERE VISION LOSS)
• CHOROIDAL NEOVASCULARIZATION – DEFINED BY THE PRESENCE OF ANGIOGENIC
VESSELS THAT PRESUMABLY ORIGINATE FROM THE CHORIOCAPILLARIS AND PENETRATE
THROUGH BRUCH’S MEMBRANE; THE VESSELS MAY LEAK AND THE EXUDED BLOOD
ORGANIZED BY RETINAL PIGMENT EPITHELIAL CELLS INTO MACULAR SCARS