NEUROPATHY

ALDY S. RAMBEDEPARTEMEN NEUROLOGI FK USU/DEPARTEMEN NEUROLOGI FK USU/

RSUP H. ADAM MALIK MEDAN

DEFINITION

Neuropathy is defined as a disease ori j f th i h l tinjury of the peripheral sensory, motor, or autonomic nerves.Can be : - pure motor

- pure sensorypure sensory- mixed sensorimotor

t i- autonomic

CategoryUsually categorized separately :

N th l ti i j t thNeuronopathy : selective injury to the cell body of the axonRadiculopathy : selective injury to the nerve roots distal to their originPlexopathy : injury to the brachial or lumbosacral plexusp

CLASSIFICATION

1. BASED ON THE ONSET OF NEUROPATHY:

ACUTE NEUROPATHYeg. : ACUTE IDIOPATHIC POLYNEUROPATHYCHRONIC NEUROPTHYeg. : BERI BERI

DIABETES MELLITUSLEPROSY

2. BASED ON SEVERITY

1. MILD NEUROPATHY :SENSORY ONLY

2. MODERATE NEUROPATHY :SENSORY MOTOR AND DECREASE OFSENSORY, MOTOR, AND DECREASE OF TENDON REFLEXES

3. SEVERE NEUROPATHY :3. SEVERE NEUROPATHY :SENSORY, MOTOR, DECREASE OF TENDON REFLEXES, MUSCLE ATROPHY

3. BASED ON THE NUMBER OF NERVES INVOLVEDNERVES INVOLVED

1. MONONEUROPATHY SIMPLEX : ONLY ONE PHERIPHERAL NERVE INVOLVED.

2. MONONEUROPATHY MULTIPLEX (MULTIFOCAL NEURPATHY) : )MULTIPE, SCATTERED NERVES IN AN IRREGULAR DISTRIBUTION

3. POLYNEUROPATHY : SEVERAL NERVES INVOLVED, SYMMETRICAL, SAME ONSET AND DISTAL PREDOMINANT.SAME ONSET AND DISTAL PREDOMINANT.

4. BASED ON LESION SITE

1 DISTAL AXONOPATHY : AXONAL LESION

2. MYELINOPATHY : DISORDER OF MYELIN SHEATH.

3. NEUROPATHY :DISORDER OF CELL BODY AT ANTERIOR HORN CELLS, SPINAL CORD OR DORSAL ROOT GANGLION.

ETIOLOGY1. IDIOPATHIC INFLAMMATORY NEUROPATHIES

- ACUTE IDIOPATHIC POLYNEUROPATHY(GUILLAIN BARRE SYNDROME)

- CHRONIC INFLAMMATORY DEMYELINATING POLYNEUROPATHY

2. METABOLIC AND NUTRITIONAL NEUROPATHIES- DIABETES, HYPOTHYROIDI, ACROMEGALY, ,- UREMIA- LIVER DISEASES- VIT B1, OR VIT B12 DEFICIENCYVIT B1, OR VIT B12 DEFICIENCY

ETIOLOGY

3. INFECTIVE AND GRANULOMATOUS NEUROPATHIES:AIDS, LEPROSY. DIPHTHERY, SARCOIDOSIS

4. VASCULITIS NEUROPATHIES:POLYARTERITIS NODOSA- POLYARTERITIS NODOSA

- RHEUMATOID ARTHRITIS- SYSTEMIC LUPUS ERYTHEMATOSUSSYSTEMIC LUPUS ERYTHEMATOSUS

ETIOLOGY

5. NEOPLASTIC AND PARAPROTEINEMIC NEUROPATHIES:- COMPRESSION AND IRITATION BY TUMOR- PARANEOPLASTIC SYNDROME- PARAPROTEINEMIAS- AMYLOIDOSIS

ETIOLOGY

6. DRUGS INDUCED AND TOXIC NEUROPATHIES- DAPSONE, ISONIAZIDE, PHENYTOIN,

PIRIDOXYNE, VINCRISTIN, HIDRALAZINE.- ALCOHOL- TOXINS : ORGANOPHOSPHAT- TOXINS : ORGANOPHOSPHAT

ARSENICLEADTHALIUMGOLD

ETIOLOGY (cont.d)

7. HEREDITARY NEUROPATHIES- IDIOPATHIC

HEREDITARY MOTOR AND SENSORY NEUROPATHIESHEREDITARY SENSORY NEUROPATHIESFAMILIAL AMYLOIDOSIS

- METABOLICPORPHYRIAPORPHYRIAMETACHROMATIC LEUCODYSTROPHYABETALIPOPROTEINEMIA

ETIOLOGY

8. ENTRAPMENT NEUROPATHIES- UPPER LIMBS

MEDIAN NERVE (CARPAL TUNNEL SYNDROME)ULNAR NERVERADIAL NERVE

- LOWER LIMBSPERONEAL NERVEPERONEAL NERVEFEMORAL NERVEOBTURATOR NERVE

PATHOGENESISCan be divided into 4 major categories :1. Neuronal degeneration : results from damage to the motor or

ll b di i h b d isensory nerve cell bodies, with subsequent degeneration2. Wallerian degeneration : results from damage to the axon at

a specific point below the cell body, with degeneration distal t th i jto the injury.

3. Axonal degeneration : results from diffuse axonal damage. The distal portion undergoes the earliest and most severe h f ll d b d l i l t ith ti dchange followed by gradual proximal ascent with continued

injury (dying back phenomenon)4. Segmental demyelination : results from injury to the myelin

h th ith t i j t thsheath without injury to the axon

PATHOPHYSIOLOGY

1 NEUROPRAXIS1. NEUROPRAXIS :- the mildest form- conduction disruption only- intact nerve continuityy- recovery in minutes or weeks

PATHOPHYSIOLOGY

2. AXONOTMESIS:AXONAL DAMAGE FOLLOWED BY- AXONAL DAMAGE FOLLOWED BY DEGENERATION

- ENDONEURAL SHEATH REMAINS INTACTINTACT

- POSSIBLE REGENERATION

PATHOPHYSIOLOGY

3. NEUROTMESIS:

- PARTIAL OR TOTAL NERVE DAMAGESURGICAL INTERVENTION IS NEEDED- SURGICAL INTERVENTION IS NEEDED

- 50% RECOVER

CLINICAL SYMPTOMS

1. SENSORY SYMPTOMS :Involvement of sensory axons producesInvolvement of sensory axons produces impairment of sensation with dysesthesias or paresthesias.

CLINICAL SYMPTOMS

2. MOTOR SYMPTOMS :Involvement of motor axons produces muscleInvolvement of motor axons produces muscle wasting and weakness followed by atrophy and fasciculations

- LMN TYPE MUSCLE WEAKNESS- FOOT DROP- WRIST DROPWRIST DROP

CLINICAL SYMPTOMS

3. CHANGE OF TENDON REFLEXESThe tendon reflexes supplied by theThe tendon reflexes supplied by the affected nerve are depressed or absent.

decreased or absent of tendon reflexesdecreased or absent of tendon reflexes

CLINICAL SYMPTOMS

4. AUTONOMIC :Involvement of axons supplying autonomicInvolvement of axons supplying autonomic function produces loss of sweating, alteration in bladder fuction, constipation, and impotencein bladder fuction, constipation, and impotence

in male

DIAGNOSIS

1. CLINICAL SYMPTOMS AND SIGNS2. LABORATORY STUDIES3. CHEST X-RAY4. LP5 ECG5. ECG6. BIOPSY : sural nerve or radial cutaneus nerve

7. ELECTROPHYSIOLOGY: EMGNCV

DIABETIC NEUROPATHYNeuropati diabetik :adanya gejala dan atau tanda disfungsi saraf perifer pd orang dgn diabetes setelah dieksklusikan penyebab lain orang dgn diabetes setelah dieksklusikan penyebab lain.

Prevalence : 10 - 20 % (symptomatic)Diabetic Neuropathy :Diabetic Neuropathy :

▫ 50% of diabetic patients ▫ type 1 than type 2 ▫ the most common : chronic sensorimotor the most common chronic sensorimotor ▫ 50% asymptomatic ▫ 10-20% needs specific treatment

PATHOGENESIS

The etiology is uncertain.

4 hypothesis (not necessarily exclusive) :1 Hyperglycemia-polyol-myoinositol1. Hyperglycemia polyol myoinositol hypothesis.2. Microvascular hypothesis3. Structural changes at the node of Ranvier.4. Vasculitic neuropathy.

DIABETIC NEUROPATHIC SYNDROMES

DISTAL SYMMETRIC NEUROPATHY :- large fiber sensory neuropathy- large fiber sensory neuropathy

numbness, paresthesias, dysesthesias, hyperesthesias ataxiahyperesthesias, ataxia.

- sensorimotor neuropathy any of the above plus distal weaknessany of the above plus distal weakness

DIABETIC NEUROPATHIC SYNDROMES

Small Fiber Neuropathy :- “pure” small fiber neuropathy

numbness, paresthesias, painful dysesthesias, hyperesthesias.

- Diabetic neuropathy cachexiaDiabetic neuropathy cachexiasubacute, severe neuropathic pain, rapid weight loss

- Autonomic neuropathyerectile dysfunction, orthostasis, cardiac dysrhythmia, diarrhea, constipationy y , , p

DIABETIC NEUROPATHIC SYNDROMES

Ischemic Mononeuropathy.- cranial (eg. CNs III, VI,VII)

diplopia, pupil-sparing third nerve palsy, hemifacial weakness

- Radicular (thoracic lumbosacral)Radicular (thoracic, lumbosacral)pain, followed by numbness or weakness in a radicular distribution

- Peripheral (eg. Femoral)pain, followed by numbness, weakness or both in territory of a single nerveboth in territory of a single nerve

DIABETIC NEUROPATHIC SYNDROMES

Regional Neuropathic Syndromes.- Diabetic amyotrophy- Diabetic amyotrophy

subacute weakness and atrophy of proximal leg musclesproximal leg muscles

- Diabetic thoracoabdominal neuropathy.subacute weakness numbness andsubacute weakness, numbness, and atrophy in thorax and abdomen

DIAGNOSIS

THERAPY

Intensive diabetic therapyM i t i id l b d i htMaintain ideal body weightAdjuvant analgetics :

TCA antidepressantscarbamazepinecarbamazepinegabapentini t lid i tintravenous lidocaine, etc

Adjuvant Analgetics

CARPAL TUNNEL SYNDROME

80% in WOMEN, A COMMON TEMPORARY PHENOMENON DURING PREGNANCYPRESSURE TO THE NERVE WHEN PASSING BENEATH THE FLEXORPASSING BENEATH THE FLEXOR RETINACULUM OBSTRUCTION OF VENOUS CIRCULATION AND EDEMA ISCHEMIA INCREASING PRESSURE ON THE NERVE ISCHEMIC ATROPHY OF NERVE FIBERSNERVE FIBERS

Etiology

1. Hereditary : HMSN type III2. Traumatic : dislocation, fracture, hematoma, wrist

sprainsprain3. Infection : tenosynovitis, tbc, sarcoidosis4. Metabolic : amyloidosis, gout5 Endocrine : acromegaly DM hypothyroidism5. Endocrine : acromegaly, DM, hypothyroidism,

pregnancy6. Neoplastic : ganglion cysts, lipoma , myeloma7 Collagen vascular diseases : RA polymyalgia7. Collagen vascular diseases : RA, polymyalgia

rheumatica, SLE8. Degenerative disease : OA9. Iatrogenic : radial artery puncture, shunt for dialysis,9. Iatrogenic : radial artery puncture, shunt for dialysis,

anticoagulant therapy

Clinical Symptoms

The earliest symptoms : numbness and paresthesias in the sensory distributionparesthesias in the sensory distribution of the median nerve in the hand (thumb, index, middle and lateral half ( , ,of the ring finger)Later on : pain, worst at nightp , gLate : inability to screw bottle caps or grip properly g p p p y

SIMPLE CLINICAL TESTS FOR CTS

PHALEN’S SIGN (PHALEN’S MANEUVRE):is present when tingling (paresthesia) is experienced in the distribution of the median nerve when the wrist is held in forced flexion (90o for 30-60 seconds)

TINEL’S SIGN (HOFFMANN-TINEL’S SIGN) :is present when tingling (paresthesia)is experienced when tapping lightly with a finger or a tendonwhen tapping lightly with a finger or a tendon hammer over a compressed or regenerating peripheral nerve. The tingling is present in the dist ib tion of the damaged ne edistribution of the damaged nerve.

Therapy

Identified causes should be treatedCorticosteroid injection around the medianCorticosteroid injection around the median nerve in the carpal tunnel.Surgical division of the transverse ligamentSurgical division of the transverse ligament (flexor retinaculum)Endoscopic carpal tunnel releaseEndoscopic carpal tunnel release

GUILLAIN - BARRE SYNDROME (GBS)( )ESSENTIALS of DIAGNOSIS :

Rapidly progressive paralysis, often diascending

AreflexiaIncreased CSF protein without increased cellIncreased CSF protein without increased cell count (albuminocytologic dissociation)Evidence of demyelination on nerve

d ti t di ( b d l d)conduction studies (may be delayed)A neurologic emergency that may rapidly progress to respiratory compromiseprogress to respiratory compromise

GBS : Subtypes and Clinical Findings

Acute inflammatory demyelinating polyneuropathy (AIDP) :polyneuropathy (AIDP) :- ascending paralysis- minor sensory symptomsminor sensory symptoms- nonspecific antibody (Ab)- EMG/NCV : demyelination on NCS absent- EMG/NCV : demyelination on NCS, absent

F waves

GBS : Subtypes and Clinical Findings

Acute motor axonal neuropathy (AMAN) :- flaccid paralysis- flaccid paralysis- often with Campylobacter jejuni infection

IgG anti GM1 IgG anti GD1a- IgG anti-GM1, IgG anti-GD1a- EMG/NCV : reduced motor amplitudes

l t dinormal sensory studies

GBS : Subtypes and Clinical Findings

Acute motor sensory axonal neuropathy (AMSAN) :( )- acute (< 1 week)- profound quadriparesis- ventilation often required- IgG anti-GM1-EMG/NCV : reduced or absent motor amplitudes

reduced or absent sensory amplitudesaxonal injury by EMGaxonal injury by EMG

GBS : Subtypes and Clinical Findings

Miller Fisher syndrome :- ataxia- ataxia- areflexia

opthalmoplegia- opthalmoplegia- IgG anti-GQ1b

EMG/NCV d d AP- EMG/NCV : decreased sensory nerve APmotor conductions often normalnormal

GBS : SYMPTOMS AND SIGNS

AIDP often begins 1-3 weeks after an infection or inciting event such as surgery70% cases initially have paresthesias or vague70% cases initially have paresthesias or vague numbness in their hands and feet.Symmetric weakness appears a few days later and progress over days to a few weeksprogress over days to a few weeks.Paralysis is maximal by about 2 weeks in> 50% cases, and by 1 month in > 90% cases.Ascending weakness beginning in the distal legs isAscending weakness beginning in the distal legs is typical, although descending paralysis with predominant proximal muscles weakness rarely appearsappears.

GBS : SYMPTOMS AND SIGNS

Facial weakness occurs in half of patients with AIDP and ophthalmoparesis and lower cranial nerves

thi d th i d d h ineuropathies can cause dysarthriaand dysphagia.¼ AIDP require mechanical ventilationWeakness is symmetric, and ranges from mild toWeakness is symmetric, and ranges from mild to severe flaccid quadriparesis.Sensation is usually normal, despite sensory symptoms although mild distal vibratory loss may besymptoms, although mild distal vibratory loss may be found Reflexes are diminished or absentSphincter tone is normal

GBS : DIAGNOSTIC STUDIES

Imaging studies of the spinal cord to rule out myelopathic diseaserule out myelopathic disease.LP (after spinal cord disease excluded)Evaluation for infectionECGChest radiographsEMG/NCVEMG/NCV

GBS : DIFFERENTIAL DIAGNOSIS

Acute spinal cord disease (acute myelopathy, transverse myelitis)transverse myelitis)Brainstem ischemiaAcute disorders of neuromuscular junctionAcute disorders of neuromuscular junction (myasthenia gravis, botulinum intoxication)Acute neuropathies (porphiric neuropathy,Acute neuropathies (porphiric neuropathy, diphtheritic neuropathy, mononeuropathy multiplex, toxic neuropathy)

THERAPY

PLASMAPHARESIS (5-6 exchanges over 1- 2weeks) or)IMMUNOGLOBULIN IV (0,4 g/kg/day for 5days)

Equally effective when given within the first 2 weeks after onsetCombination of both no additional benefitCombination of both – no additional benefit

RCTs on oral or IV corticosteroid – failed to showRCTs on oral or IV corticosteroid failed to show benefit