Prepared by:

Dr. Sarwer Jamal Al-Bajalan

M.B.Ch.B, F.I.B.M.S(Neurology)2014

DISORDERS OF THEPERIPHERAL

NERVOUSSYSTEM

Disorders Of The Peripheral Nervous System

○ Introduction and clinical approach○ Acquired polyneuropathies(PNP)○ Hereditary neuropathies○ Mononeuritis Multiplex○ Mononeuropathies

Peripheral neuropathy: Introductionand clinical approachGeneral considerations Peripheral neuropathy or polyneuropathy: diffuse peripheral nerve lesion, often symmetrical

Mononeuropathy—lesion of a single nerve (i.e., median, femoral, or abducens). Often entrapment or trauma

Mononeuritis multiplex—focal involvement of two or more individual nerves, often asymmetric

Types and causes of peripheral neuropathy

Polyneuropathy: clinical manifestations

Age of onset varies, for example○ Childhood—CMT○ Adulthood—Diabetes○ Older adult—Paraproteinemia

Acuity of onset○ Acute—AIDP, porphyria, toxic, tick paralysis, diphtheria, vasculitis○ Chronic—B12 deficiency, paraproteinemia, diabetes, most other causes

Symptoms○ Motor symptoms—distal weakness predominates in most neuropathies. Diffi culty opening jars,

tripping over feet○ Sensory symptoms—may be

• positive (tingling, burning) or • negative (numbness).

○ Autonomic symptoms—orthostatic lightheadedness, gastroparesis, sweating abnorma ities, erectile dysfunction, tachycardia

Positive Sensory symptoms○ Paresthesia — spontaneous abnormal sensations, which

are not unduly painful

○ Dysesthesia — painful paresthesia

○ Allodynia — painful sensation resulting from a nonpainful stimulus, such as stroking, high sounds

○ Hyperesthesia — increased sensitivity to a stimulus

○ Hyperalgesia — increased sensitivity to a painful stimulus

Signs of PNPLarge-fiber neuropathy

• Loss of vibration and position sense• Diminished or absent reflexes• Positive Romberg sign• Pseudoathetosis

Small-fiber neuropathy• Loss of pain and temperature sensation• Reflexes may be normal.

Autonomic dysfunction• Miosis• Orthostatic hypotension (BP supine and erect after 3 minutes)

Cutaneous sensory loss in a stocking-glove distribution

Foot deformities such as pes cavus, pes planus, or hammertoes may indicate a hereditary neuropathy.

Nerve thickening may be seen in CMT, leprosy, Refsum disease, amyloidosis, or HNPP.

Investigations in PNP

EMG and ENGo Can distinguish polyneuropathy from polyradiculopathy or plexopathyo Can identify mononeuropathy and mononeuritis multiplexo Can distinguish axonal and demyelinating neuropathieso Can identify subclinical sensory or motor involvement

Blood tests○ I) 75 gram 2 hour oral GTT, B12, TSH, SPEP, immunofixation,

ESR, renal and liver function tests○ II) ANA, dsDNA, anti-Ro, anti-La, HIV, Lyme○ III) Others…

CSF examination; (AIDP/CIDP)

Nerve biopsy: sural, radial, superficial peroneal(vasculitis)

Investigation of peripheral neuropathy

Acquired polyneuropathies

Diabetic neuropathies Guillain–Barre syndrome (GBS) Chronic demyelinating polyneuropathy Chronic axonal polyneuropathy Brachial plexopathy Lumbosacral plexopathy Spinal Root Lesions

Diabetic neuropathies

Commonest cause of neuropathy worldwide. o 8% have neuropathy at diagnosis; o 50% after 25 years.

Diagnosiso Diabetes = fasting glucose >126, 2 hr postprandial glucose of 200 mg/dLo Impaired fasting glucose = fasting glucose 100–125 mg/dLo Impaired glucose tolerance = 2 hr postprandial glucose 140–199 mg/dL

Classification of diabetic neuropathies:

o Diabetic polyneuropathyo Diabetic neuropathic cachexiao Diabetic amyotrophyo Diabetic cranial neuropathieso Diabetic mononeuropathies

Diabetic polyneuropathy

Length dependent, painful sensory > motor neuropathyAutonomic dysfunction is common.

NCS: Show length-dependent axonal polyneuropathy. May be normal if only small fibers involved.

Rx :Foot care, Control of hyperglycemia, and Medications for neuropathic pain (i.e., gabapentin,

nortriptyline, duloxetine, pregabain).

Diabetic amyotrophyClinical manifestations

Abrupt onset of severe pain in backs, hips, and thighs followed by weakness and wasting of proximal muscles > distal muscles

Usually unilateral, but may progress to be bilateral Associated with weight loss

D Dx : Vasculitis, malignant infiltration

Investigations NCS(ENG) usually show distal sensorimotor polyneuropathy Needle EMG shows denervation in proximal lower extremity muscles

including paraspinals Consider MRI to rule out structural or infi trative process causing

radiculopathy or plexopathy

Management Spontaneous recovery over 1–3 years Methylprednisolone (1g iv tiw x 1, then qweek x 3, then q2 weeks x 4) may

speed recovery IVIG reported to be beneficial as well

Diabetic amyotrophy

Diabetic cranial neuropathies○ Oculomotor (III) palsy — pupil sparing○ Abducens (VI) palsy

Diabetic mononeuropathies DM patients are prone to entrapment syndromes. Surgery should be considered if motor involvement, but results may not be

as good as in nondiabetics.

○ Median at the wris(CTS)○ Ulnar at the elbow○ Common peroneal at the fibular neck

Guillain–Barre syndrome (GBS)

1. Acute inflammatory demyelinating polyradiculoneuropathy (AIDP)

Epidemiology: The most common cause of acute neuromuscular

weakness. Annual incidence 1–2 /100,000

Two-thirds are preceded by a GI or upper respiratory tract infection (Campylobacter jejuni, CMV, EBV, haemophilus influenzae, mycoplasma).

PathogenesisThere is a predominantly cell-mediated inflammatoryresponse directed at the myelin protein of spinal roots,peripheral and extra-axial cranial nerves, possibly triggeredby molecular mimicry between epitopes found inthe cell walls of some microorganisms and gangliosidesin the Schwann cell and axonal membranes. The resultingrelease of inflammatory cytokines blocks nerve conductionand is followed by a complement-mediateddestruction of the myelin sheath and the associatedaxon

Neurologic symptoms begin 5 days to 3 weeks after antecedent event. Ascending weakness. Proximal weakness may occur as well because

of root demyelination Early loss of reflexes Paresthesias common. Actual sensory loss is variable. Progressive over days to weeks, nadir by 4 weeks Often associated with back pain Involvement of cranial nerves can cause facial and bulbar weakness. Up to 25% have respiratory involvement requiring mechanical

ventilation. Autonomic dysfunction (hypotension, hypertension, cardiac arrhythmia)

Clinical features

Diagnostic studiesNCS: May be normal early in the course of the disease

Prolongation of F-responses, Prolongation of motor latencies, and Prolongation of motor conduction velocities. Conduction block correlates with degree of weakness.

CSF:Elevation of protein (may be normal first 10 days). Little or no CSF pleocytosis, unless associated with HIV or

Lyme.

Management

IVIG 0.4 g/kg/day x 5 days

Plasma exchange (2–5 exchanges, depending on the severity of the disease)

No benefit from corticosteroids

Supportive measures

○ Follow vital capacity (VC) and negative inspiratory force (NIF

○ Transfer patient to the I CU and consider elective intubation IF:

fVC <20 mL/kg (1.5 L for an average adult) or

NIF is worse than –30 cm H2O,

○ Do not wait for O2 saturation or PO2 to drop.

○ Swallowing assessment

○ Cardiac monitoring in all patients who are severely affected, at least until they start to improve.

○ Treat neuropathic pain

- (gabapentin, pregabalin, or tramadol).

- Avoid tricyclic antidepressants early, which may lower threshold for arrhythmia.

○ DVT prophylaxis

○ Bowel regimen for constipation

○ Physical therapy to prevent contractures and speed recovery of function

Prognosis Overall, 80% of patients recover completely within 3–6 months.

Untreated, about 35% of patients have residual weakness, atrophy, hyporeflexia, and facial weakness.

Partial recovery followed by relapse occur in <10% of patients.

Recurrence after full recovery is 2%.

Mortality is 4 %.

Poor outcome associated with○ Older age○ Preceding diarrheal illness○ Rapid deterioration and severe weakness○ Electrically inexcitable nerves and muscle wasting (axonal loss)

Other Variants of GBS2. Acute motor axonal neuropathy (AMAN)

○ Little or no demyelination○ Often associated with Campylobacter jejuni infection○ A subset of patients will recover rapidly

3. Acute motor sensory axonal neuropathy (AMSAN)○ Little or no demyelination○ Poorer prognosis than AIDP and AMAN

3. Miller Fisher syndrome○ Ophthalmoplegia○ Ataxia○ Areflexia○ Associated with GQ1b antibody

4. Acute sensory neuropathy

6. Acute pandysautonomia

Chronic polyneuropathy A chronic symmetrical polyneuropathy, evolving over months or

years, is the most frequently seen form of neuropathy.

In about 30% of patients no cause can be established, even after thorough investigation.

These patients usually have a mild axonal neuropathy which, whilst causing unpleasant symptoms, does not lead to motor disability.

Therefore, if a patient with what seems to be an idiopathic polyneuropathy progresses to significant disability, further thought needs to be given to finding a specific cause (usually inflammatory or genetic).

Chronic Demyelinating Polyneuropathy

This type of chronic polyneuropathy is often : Hereditary or Immune -mediated (including those caused by abnormal paraproteins).

Causes:

○ Hereditary○ CIDP○ Lymphoma○ Osteoclastic myeloma○ IgM paraproteinaemia○ Arsenic toxicity○ Amiodarone toxicity○ Diphtheria

Heriditary Demyelinating Polyneuropathy Many inherited disorders cause demyelinating peripheral

neuropathies and one of the best known is Charcot–Marie–Tooth disease (CMT).

This neuropathy produces:

○ Distal wasting (‘inverted champagne bottle’ or ‘stork’ legs), ○ Often with pes cavus, and ○ Predominantly motor clinical involvement.

○ In 70–80% the cause is duplication of the PMP-22 gene on chromosome 17 (autosomal dominant CMT type 1)

○ Similar phenotypes are produced by mutations in other genes with differing modes of inheritance

CMT

Pes cavus, Inverted champagne bottole, Samll muscle atrophy

Hereditary peripheral neuropathies

Hereditary demyelinating neuropathies

Chronic Inflammatory Demyelinating Polyradiculopathy (CIDP) Presents with a relapsing or progressive generalised neuropathy.

Sensory, motor or autonomic nerves can be involved but the signs are predominantly motor;

A variant causes only motor involvement (multifocal motor neuropathy, MMN).

RX

Immunosuppressive treatment:Corticosteroids ,

Methotrexate or

Cyclophosphamide , or

Plasma exchange

Intravenous immunoglobulin, IVIG

MMN is best treated by IVIG.

Some 10% of patients with acquired demyelinating polyneuropathy have an abnormal serum

paraprotein, sometimes associated with a lymphoproliferative malignancy.

Treatment flowchart for CIDP

Chronic axonal polyneuropathy

This is the most common type of chronic polyneuropathy.

Where the cause can be found, it is usually a disorder affecting axonal metabolism and transport, either acquired (drugs and toxins) or genetically determined

○ Metabolic/endocrine diseases (including diabetes)○ Alcohol○ Drugs and toxins○ Vitamin deficiency○ Hereditary○ IgG paraproteinaemia○ Paraneoplastic○ Primary amyloidosis

Brachial plexopathy Trauma usually damages either the upper or the lower parts of the brachial plexus,

according to the mechanics of the injury. The clinical features depend upon the anatomical site of the damage .

Causes of Lower Brachial Plexopathy:○ Infiltration from breast or apical lung tumours (Pancoast tumour).○ Therapeutic irradiation○ Thoracic outlet syndrome: which may be accompanied by circulatory changes in the arm due to

subclavian artery compression.

Brachial plexus anatomy: L, lateral; M, medial; P, posterior

Neuralgic Amyotrophy

An acute brachial plexopathy of probable inflammatory origin.

In this syndrome, a period of very severe shoulder pain precedes the appearance of a patchy upper brachial plexus lesion.

Often affecting the long thoracic nerve which produces winging of the scapula.

Recovery occurs over months and is usually complete.

Lumbosacral plexopathy

May be caused by: Neoplastic infiltration or

Compression by retroperitoneal haematomas in patients with a coagulopathy.

A small vessel vasculopathy can produce a lumbar plexopathy,

especially in elderly patients when it may be the presenting feature of;

○ Type 2 diabetes mellitus (‘diabetic amyotrophy’) or ○ A vasculitis.

Spinal Root Lesions

Compression at or near their spinal exit foramina by prolapsed intervertebral discs or degenerative spinal disease.

Infiltration by spinal and paraspinal tumour masses and

Inflammatory or infective processes.

The clinical features include:

○ Muscle weakness and wasting and ○ Dermatomal sensory loss with ○ Reflex changes that reflect the pattern of roots involved. ○ Pain in the muscles whose innervating motor roots are involved.

Mononeuritis Multiplex Lesions of multiple nerve roots, peripheral nerves or cranial nerves.

It is due either to involvement of the vasa nervorum or to malignant infiltration of the nerves.

The clinical expression of a very widespread multifocal neuropathy may become confluent so that the clinical picture eventually resembles a polyneuropathy.

In this case neurophysiology may be required to identify the multifocal nature of the problem.

Causes of Mononeuritis Multiplex

Infections:○ Lyme disease○ Leprosy○ Acute viral hepatitis A○ Hepatitis B○ Hepatitis C○ Acute parvovirus B-19 infection○ Herpes simplex virus infection○ AIDS and HIV infection

Rheumatological:○ Wegener granulomatosis○ Henoch-Schönlein syndrome○ Sjögren syndrome○ Behçet’s disease○ Temporal (giant cell) arteritis○ Systemic lupus erythematosus○ Rheumatoid arthritis○ Polyarteritis nodosa○ Scleroderma

Chronic:○ Diabetes mellitus○ Amyloidosis[8]

○ Neurosarcoidosis[36, 37]

Cancer -related:○ Chronic graft versus host disease (GVHD)○ Direct tumor invasion with intraneural

spread of Lymphoma 

○ B-cell leukemia 

○ carcinoid tumor○ Paraneoplastic – Small cell lung cancer

Hematologic:○ Churg-Strauss syndrome○ Hypereosinophilia○ Cryoglobulinemia○ Hypereosinophilia○ Atopy-related peripheral neuritis○ Idiopathic thrombocytopenic purpura

Miscellaneous:○ Amphetamine angiitis○ Gasoline sniffing○ Genetic disorder; Tangier disease.○ Multiple compression neuropathies.

Mononeuropathies

Facial mononeuropathy (Bell palsy)

Weakness: Upper and lower face, inability to close the eye, mouth drawn to the affected side.

Patients often describe the face as ‘numb’, but there is no objective somatosensory loss.

Loss of direct & consensual corneal reflex on the affected side. Decreased tearing, hyperacusis, and loss of taste to the anterior two thirds of the

tongue may be present. Onset is sudden, usually over hours.

EMG/NCV are rarely necessary to make the diagnosis, but can be used to determine prognosis.

DDx: Herpes zoster, HIV, Lyme, facial tumor, sarcoidosis & neuro-brucellosis.

Rx Artificial tears, protective goggles, eye patch at night Prednisone 40–60 mg/d for a week ; speeds recovery if started within 72 hrs. Anti-virals probably not beneficial?? ( Acyclovior 400x5 for 10 days)

Rt LMN VII palsy Prognosis some recovery within 3

weeks(85%). Complete recovery(75%)

Poor recovery predicted if: Complete paralysis, Older age Comorbidity; DM , HTN Hyperacusis Loss of taste for > 1wk Reto-auricular pain Axonal loss

Aberrant re-innervation may occur during recovery, producing unwanted facial movements such as eye closure when the mouth is moved, or ‘crocodile tears’ (tearing during salivation).

Hemifacial spasm 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.

The spasms are exacerbated by talking or eating, or when the patient is under stress.

The cause is probably an aberrant arterial loop irritating the nerve just outside the pons.

The facial nerve should be imaged to exclude a structural lesion, especially in a young patient.

Treatment oDrug is not effective. oBotulinum toxin (repeated every 3 months). oMicrovascular decompression.

Hemifacial spasm.MOV

Trigeminal Nerve Lesions

Isolated trigeminal sensory neuropathy is rare. It causes unilateral facial sensory loss and is associated in some patients with;

oscleroderma, oSjögren’s syndrome or oother connective tissue disorder.

Trigeminal neuralgia do not have sensory loss on examination unless there have been operative procedures on the nerve.

Herpes Zoster (most frequently in the ophthalmic division) and is followed in about one-third of patients by postherpetic neuralgia).

Herpes Zoster Ophthalmicus

Entrapment neuropathy

Focal compression or entrapment is the usual cause of mononeuropathy.

The pressure damages the myelin sheath slowing NCS.

Sustained or severe pressure axonal loss loss of sensory AP distal to the site of compression.

Causes: Acromegaly , Hypothyroidism , Pregnancy Diabetes Osteophytes HNPP(hereditary neuropathy with liability to pressure palsies)

- multiple recurrent entrapment neuropathies, - especially at unusual sites- autosomal dominant

Symptoms and signs in common Entrapment Neuropathies

Median at wrist (CTS) Ulnar at elbow Meralgaia Paraesthetica

Differential diagnosis by pattern of symptomsPattern 1: Symmetrical proximal and distal weakness with sensory loss. (Consider CIDP, vasculitis.)Pattern 2: Symmetrical distal weakness with sensory loss. (Consider diabetes, drugs and toxins, hereditary neuropathies,

amyloidosis, paraproteinemia.)Pattern 3: Asymmetric distal weakness and numbness. (Consider vasculitic neuropathy, HNPP, infectious neuropathy, multifocal

trauma or entrapment.)Pattern 4: Asymmetric distal or proximal weakness without sensor loss. (Consider multifocal motor neuropathy, motor neuron

disease, inclusion body myositis.)Pattern 5: Asymmetric proximal and distal weakness with sensory loss. (Consider polyradiculopathy or plexopathy, ma ignant infi

ltration, brachial neuritis, HNPP.)Pattern 6: Symmetric small fiber sensory neuropathy without weakness. (Consider diabetes, Fabry disease, amyloidosis, HIV.)Pattern 7: Symmetric small and large fiber sensory neuropathy without weakness. (Consider diabetes, drugs, toxins,

paraproteinemia.)Pattern 8: Marked proprioceptive sensory loss. (Consider paraneoplastic, B6 toxicity, Sjogren, HIV.)Pattern 9: Autonomic predominant. (Consider autoimmune, amyloidosis, diabetes, AIDP.)Pattern 10: Neuropathy with cranial nerve involvement. (Consider Lyme, HIV, AIDP, sarcoidosis, malignant infiltration, Tangier

disease, trichloroethylene toxicity, anti-Gd1b neuropathy.)