Dr. Mohammad Shaikhani Assistant professor Sulaimani University College of Medicine. DISEASES OF THE PERIPHERAL NERVOUS SYSTEM:
Neuropathies:Introduction: <ul><li>Nerve dysfunction caused by many inherited& acquired diseases. </li></ul><ul><li>Can affect the nerve roots (radiculopathy), nerve plexuses (plexopathy) , individual nerves (neuropathy) or Cranial nerves (cranial neuropathy). </li></ul><ul><li>Nerve fibres of different types (motor, sensory or autonomic) & of different sizes may be variably involved. </li></ul><ul><li>Disorders may be primarily directed at the axon, the myelin sheath (Schwann cells) or both. </li></ul><ul><li>Of 3 types: </li></ul><ul><li>1.Mononeuriits. </li></ul><ul><li>2.Mononeuritis multiplex. </li></ul><ul><li>3. Cranial neuropathies. </li></ul><ul><li>4.Polyneuropathy. </li></ul>
FOCAL NEUROPATHY (MONONEUROPATHY): <ul><li>Entrapment is the usual cause of a mononeuropathy, but a. </li></ul><ul><li>A may present with a single nerve lesion but later develops into multiple nerve lesions (clinically or neurophysiologically), i.e. a multifocal neuropathy (mononeuritis multiplex). </li></ul>
Entrapment neuropathies <ul><li>Pressure mild or intermittent initially damages myelin sheath& NCS will show slowing of conduction over the relevant site. </li></ul><ul><li>Sustained or severe pressure damages the integrity of the axons , with loss of the sensory action potential distal to the compression. </li></ul><ul><li>Certain conditions increase susceptibility to develop entrapment neuropathies as: acromegaly, hypothyroidism, pregnancy, any pre-existing mild generalized axonal neuropathy (e.g. DM)& bone damage near the nerve. </li></ul><ul><li>Patients with multiple recurrent entrapment neuropathies, esp at unusual sites, should be screened for AD hereditary neuropathy with liability to pressure palsies (HNPP). </li></ul><ul><li>Unless axonal loss has occurred, entrapment neuropathies will recover if the pressure relieved, either by avoiding precipitating activities or limb positions, or by surgical decompression. </li></ul>
Entrapment neuropathies Lateral border of thigh Nil Tingling / dysaesthesia on lateral border of the thigh Lateral cutaneous nerve of the thigh (meralgia paraesthetica) Nil or dorsum of foot Dorsiflexion and eversion of foot Foot drop, trauma to head of fibula Peroneal Dorsum of thumb Wrist and finger extensors, supinator Weakness of extension of wrist and fingers, often precipitated by sleeping in abnormal posture, e.g. arm over back of chair Radial Medial palm & little finger& medial half 4th finger All small hand muscles, excluding abductor pollicis brevis Paraesthesia on medial border of hand, wasting & weakness of hand muscles Ulnar (at elbow) Lateral palm & thumb, index, middle and medial half 4th finger Abductor pollicis brevis Pain /d paraesthesia on palmar aspect of hands &fingers, waking the patient from sleep. Pain may extend to arm and shoulder Median (at wrist) (carpal tunnel syndrome) Area of sensory loss Muscle weakness/muscle-wasting Symptoms Nerve
Investigations in NEUROPATHIES: Genetic screening tests (e.g. hereditary neuropathies, Friedreich's ataxia) Chest X-ray/CT Mammogram, Abd imaging Nerve conduction/EMG Other Antineuronal antibodies Serum autoantibodies (ANF, dsDNA, RF, extractable nuclear antigens) Antiganglioside antibodies VDRL Immunology Urinary Bence Jones protein Faecal occult blood Plasma protein electrophoresis Urinary porphyrins Thyroid function tests Prostate-specific antigen FBS,GTT/HbA lc Toxic metal / drug screen Liver function tests Phytanic acid (Refsum's disease) Cryoglobulins Creatinine Vit as B12,E Serum lipids, lipoproteins Urea, electrolytes, calcium Biochemistry B 12 / folate ESR Full blood count Haematology Occasionally useful tests Second-line tests First-line tests
CRANIAL NEUROPATHIES: Trigeminal neuropathy <ul><li>Isolated trigeminal sensory neuropathy is rare. </li></ul><ul><li>It causes unilateral facial sensory loss & associated in some patients with scleroderma, Sjögren's syndrome, or other connective tissue disorder. </li></ul><ul><li>Patients with trigeminal neuralgia do not have sensory loss on examination unless there have been operative procedures on the nerve, frequently caused by aberrant vessel in the nerve orign & can be treated neurosurgicaly, medical treatment is by antiepileptic drugs as carbamezipine . </li></ul><ul><li>Reactivation of varicella virus in the trigeminal nerve causes herpes zoster (most frequently in the ophthalmic division) & is followed in 1/3 by post-herpetic neuralgia. </li></ul>
Cranial neuropathies: Idiopathic isolated facial nerve palsy (Bell's palsy) <ul><li>This is a common condition affecting all ages & both sexes. </li></ul><ul><li>The lesion is within the facial canal & may be due to reactivation of latent herpes simplex virus 1 infection. </li></ul><ul><li>Symptoms usually develop subacutely over a few hours, with pain around the ear preceding the unilateral facial weakness. </li></ul><ul><li>Patients often describe the face as 'numb', but there is no objective sensory loss (except possibly to taste). </li></ul><ul><li>Hyperacusis can occur if the nerve to stapedius is involved& there may be diminished salivation & tear secretion. </li></ul><ul><li>Exam: ipsilateral lower motor neuron facial nerve palsy. </li></ul><ul><li>Vesicles in the ear or on the palate indicate that the facial palsy is due to herpes zoster rather than Bell's palsy. </li></ul>
Cranial neuropathies: Idiopathic isolated facial nerve palsy (Bell's palsy) <ul><li>1/3 of acute peripheral facial weakness are caused by: </li></ul><ul><li>Trauma. </li></ul><ul><li>DM. </li></ul><ul><li>HT. </li></ul><ul><li>Eclampsia. </li></ul><ul><li>Ramsay Hunt syndrome (facial palsy with zoster oticus caused by varicella–zoster virus) </li></ul><ul><li>Lyme disease. </li></ul><ul><li>Sarcoidosis, Sj ِ gren’s syndrome </li></ul><ul><li>Parotid gland tumors. </li></ul><ul><li>Amyloidosis </li></ul><ul><li>Complication of intranasal influenza vaccine. </li></ul><ul><li>The remaining 2/3 are idiopathic (Bell’s palsy). </li></ul>
Bell's palsy: management <ul><li>Prednisolone 40-60 mg daily for a week may speed recovery if started within 72 hours </li></ul><ul><li>Aciclovir(Zovirax) also recommended. </li></ul><ul><li>Aciclovir alone is not as effective as corticosteroids, but aciclovir+ prednisolone more effective than steroids alone . </li></ul><ul><li>Valacyclovir, a prodrug completely converted to acyclovir &L-valine with increased bioavailability, but more costy & its use with GCs could be considered in severe or complete facial palsy. </li></ul><ul><li>Artificial tears / ointment prevent exposure keratitis & the eye should be taped shut overnight. </li></ul><ul><li>About 80% of patients recover spontaneously within 12 weeks. </li></ul><ul><li>Aberrant re-innervation may occur during recovery, producing unwanted facial movements (e.g. eye closure when the mouth is moved) or 'crocodile tears' (tearing during salivation). </li></ul><ul><li>Recurrences can occur but should prompt further investigation. </li></ul>
Bell's palsy: Bad prognostic signs <ul><li>A slow or poor recovery is predicted by: </li></ul><ul><li>Complete paralysis. </li></ul><ul><li>Older age. </li></ul><ul><li>Reduced facial motor action potential amplitude after 1st week. </li></ul>Sir Charles Bell
Cranial neuropathies: Hemifacial spasm <ul><li>Usually presents after middle age with intermittent twitching around one eye, spreading ipsilaterally over months or years to affect other parts of the facial muscles. </li></ul><ul><li>The spasms are exacerbated by talking or eating, or when the patient is under stress. </li></ul><ul><li>The cause, as trigeminal neuralgia, is an aberrant arterial loop irritating the nerve just outside the pons. </li></ul><ul><li>The facial nerve should be imaged to exclude a structural lesion, as tmors especially in a young patient. </li></ul><ul><li>Drug treatment is not effective but injections of botulinum toxin into affected muscles help& usually have to be repeated every 3 months. </li></ul><ul><li>Occasionally, microvascular decompression is necessary </li></ul>
MULTIFOCAL NEUROPATHY (MONONEURITIS MULTIPLEX) <ul><li>When multiple nerve root, peripheral nerve or cranial nerve lesions occur serially or concurrently, the pathology is due either to involvement of the vasa nervorum (vasculitis or DM) or malignant infiltration of the nerves. </li></ul><ul><li>The clinical expression of a very widespread multifocal neuropathy may become confluent so that the clinical picture eventually resembles a polyneuropathy. </li></ul><ul><li>In this case neurophysiology may be required to identify the multifocal nature of the problem. </li></ul><ul><li>Investigation of patients with an acute multifocal neuropathy should be urgent since vasculitis is a common cause, either as part of a systemic disease or isolated to the nerves. </li></ul>
GENERALISED NEUROPATHY (POLYNEUROPATHY) <ul><li>The clinical effects of a generalised pathological process occur in the longest peripheral nerves first, affecting the distal lower limbs before the upper limbs, with sensory symptoms & signs of an ascending 'glove/stocking' distribution. </li></ul><ul><li>This is particularly true with axonal neuropathies where the disorder affects the metabolic processes required for axonal transport in the peripheral nerves as DM. </li></ul><ul><li>In inflammatory demyelinating neuropathies, the pathology may be more patchy & variations from this ascending pattern occur. </li></ul><ul><li>Generalized neuropathies may be acute or chronic. </li></ul>
ACUTE INFLAMMATORY DEMYELINATING POLYNEUROPATHY AIDP (GUILLAIN-BARRé SYNDROME) <ul><li>Develops 1-4 weeks after respiratory infection or diarrhoea (particularly Campylobacter ) in 70%. </li></ul><ul><li>There is a predominantly cell-mediated inflammatory response directed at the myelin protein of spinal roots, peripheral & cranial nerves, triggered by molecular mimicry between epitopes found in the cell walls of some micro-organisms & gangliosides in the Schwann cell membranes. </li></ul><ul><li>The resulting release of inflammatory cytokines blocks nerve conduction followed by a complement-mediated destruction of the myelin sheath &the associated axon, if it is severe. </li></ul>
GUILLAIN-BARRé SYNDROME: Clinical features <ul><li>Distal paraesthesia & limb pains (often severe) precede a rapidly ascending muscle weakness, from lower to upper limbs, more marked proximally than distally. </li></ul><ul><li>Facial / bulbar weakness commonly develops& respiratory weakness requiring ventilatory support occurs in 20%. </li></ul><ul><li>In most patients, weakness progresses for 1-3 weeks, but rapid deterioration to respiratory failure can develop within hours. </li></ul><ul><li>On exam: diffuse weakness with widespread loss of reflexes. </li></ul><ul><li>An unusual variant; Miller Fisher type: triad of ophthalmoplegia, ataxia & areflexia. </li></ul><ul><li>Bilateral LMN fascial palsy occur in 50%. </li></ul><ul><li>An axonal variant, rare in Europe /North America but more common in China / Japan in which irculating antibodies to various peripheral nerve gangliosides are often found. </li></ul>
GUILLAIN-BARRé SYNDROME: Investigations <ul><li>The CSF protein is elevated at some stage of the illness but may be normal in the first 10 days. </li></ul><ul><li>There is usually no rise in CSF cell number (a lymphocytosis of > 5 × 107 cells/litre suggests an alternative diagnosis). </li></ul><ul><li>Electrophysiological studies are often normal in the early stages but show typical changes after a week or so, with conduction block & multifocal motor slowing, sometimes most evident proximally as delayed F-waves. </li></ul><ul><li>Investigation to identify an underlying cause, as CMV, mycoplasma or Campylobacter , requires a chest X-ray, stool culture & appropriate immunological blood tests. </li></ul><ul><li>Antibodies to the ganglioside GQ1b are found in the Miller Fisher variant. </li></ul><ul><li>Acute porphyria should be excluded by urinary porphyrin& serum lead should be measured if there are only motor signs. </li></ul>
GUILLAIN-BARRé SYNDROME: prognosis <ul><li>Overall, 80% of patients recover completely within 3-6 months, 4% die& the remainder suffer residual neurological disability which can be severe. </li></ul>
GUILLAIN-BARRé SYNDROME: bad prognostic factors <ul><li>Older age. </li></ul><ul><li>Rapid deterioration to ventilation. </li></ul><ul><li>Evidence of axonal loss on EMG. </li></ul>
GUILLAIN-BARRé SYNDROME: Management <ul><li>During the phase of deterioration, regular monitoring of respiratory function (vital capacity /arterial blood gases) is required, as respiratory failure may develop with little warning & require ventilatory support. </li></ul><ul><li>Ventilation may be needed if the vital capacity < 1 litre, but intubation is more often required because of bulbar incompetence leading to aspiration. </li></ul><ul><li>General management & physiotherapy to protect the airway ,prevent pressure sores &venous thrombosis is essential. </li></ul><ul><li>Corticosteroid ineffective, but, plasma exchange & IV immunoglobulin shorten the duration of ventilation & improve prognosis, provided treatment is started within 14 days of the onset of symptoms, but no advantage of combining both. </li></ul>
Chronic inflammatory demyelinating polyneuropathy (CIDP) <ul><li>Either hereditary,metabolic as DM or immune-mediated (including abnormal paraproteins). </li></ul><ul><li>Many abnormal genotypes cause hereditary demyelinating peripheral neuropathies with variable phenotypes, most characteristically that known as Charcot-Marie-Tooth (CMT) produces distal wasting ('inverted champagne bottle' or 'stork' legs), often with pes cavus&a predominantly motor clinical involvement. In 70-80% PMP-22 gene on chromosome 17 (autosomal dominant CMT type 1). </li></ul>
CIDP <ul><li>Presents with a relapsing or progressive generalised neuropathy. </li></ul><ul><li>Sensory, motor or autonomic nerves can be involved but the signs are usually predominantly motor; a variant causes only motor involvement (multifocal motor neuropathy, MMN). </li></ul><ul><li>Usually responds to immunosuppressants; corticosteroids or cyclophosphamide, or to immunomodulators (plasma exchange or IV immunoglobulin, IVIg). </li></ul><ul><li>MMN is best treated by IVIg. </li></ul><ul><li>10% of patients with acquired CIDP have an abnormal serum paraprotein, sometimes associated with a lymphoproliferative malignancy. </li></ul>
Chronic symmetrical polyneuropathy <ul><li>Evolving over months or years, is the most frequently seen form of neuropathy. </li></ul><ul><li>In 30% of patients no cause can be established, even after thorough investigation. </li></ul><ul><li>These patients usually have a mild axonal neuropathy , causing unpleasant symptoms, but does not lead to motor disability. </li></ul><ul><li>If a patient with what seems to be an idiopathic polyneuropathy progresses to significant disability, finding a specific cause (usually inflammatory or genetic or metabolic as DM) needed. </li></ul>
Myopathies: hereditary Gower sign Calf p hypertrophy Winging scapula Type Inheritance . Age at onset. Muscles affected & associated signs. Duchenne MD. Becker Limb girdle. Fascio scapulo humeral Myotonia dystrophica. X linked Res. = AutosoRes. Autoso dominan Autosom D. 3 to 10 ys. Older 10 to 30 ys. 10 to 40. Any( 20 to 60) Proximal legs & arms ,then generalized. Pelvic or shoulder girdle or both. Less sever,may reach adulthood. Fascial ,shoulder & seratous anterior. Temporalis, fascial, sternocleidomastoid, distal limbs ptosis, catarct, testicular atrophy, frontal baldness & myotonia(slow relaxation of contracting muscles).
Diagnosis : Muscle enzymes as CPK –MM (myocardial band) which is very high in Duchenne & normal or moderately increased in others. EMG &muscle biopsy. Management: No specific treatment except for physiotherapy & rehabilitation ,although there reports of benefit of steroids in DMD. Genetic counseling: DMD & Myotonia Dyst. Can now be diagnosed by DNA analysis even in the preclinical period or in female carriers or during pregnancy Appropriate advice can be offered to couples before marriage or before deciding to have a child or to decide on abortion .
Prognosis : DMD & Myotonia Dystr. Die with HF & respiratory failure DMD within 10 years of diagnosis life span of FSH & limb girdle is not affected.
Toxic myopathies : Caused by: toxins as alcohol drugs as carbinoxolone, thiaxide, diuretics, steroids & penicilamine. Metabolic & endocrine myopathies: Causes of acute muscle weakness : Electrolyte abnormalities as hypo & hyperkalemia , hypo & hypercalcemia familial periodic paralysis which may be hypokalemic, normokalemic or hyperkalemic. Causes of chronic metabolic or endocrine proximal myopathies affecting proximal shoulder & pelvic girdle include: hyperthyroidism , hypothyroidism, cushing , Addison & it may be the first presentation of endocrine disorders .