NEUROMUSCULO SKELETAL

Dr. Jumraini Tammasse, SpS.

NEUROPATHY
NEUROPATHY Definition (WHO, 1980) Permanent dysfunction (more than several hours) Spinal neurons, cranial neurons Motoric, sensoric, or autonomic Confirmed by clinical evidence and/or electroneurographic or morphplogic (Pathologic Anatomy) evidence

Classification
1.

Dominant clinical features

Motoric Sensoric Autonomic Compound

2.

Anatomical Distribution

Symmetrical distal (polineuropathy) Multiplex mononeuropathy Radiculopathy Localized neuropathy

3. Onset and course of disease

Acute Sub

acute Chronic Recurrent

4. Prominent pathological features

Axonopathy
Myelinopathy Other

features

AXONAL NEUROPATHY
Axons are disturbed with secondary effect to myelin Large axons attacked first Ischaemia causes vasculopathy

DEMYELINATING NEUROPATHY

Attacks schwann cells of myelin sheaths, causes demyelinating of peripheral axons, segmental distribution (between nodes of Ranvier)

COMPOUND TYPE Most neuropathies are compound type, where myelin are attacked more than axons, or axons are atacked more than myelin This compound type can be divided as :

Primary axonal degeneration with secondary segmental demyelination , e.g. uremic polineuropathy. Primary myelin degeneration followed by axonal degeneration, e.g. polineuropathy caused by diphteria infection.

Commonly, its difficult to differentiate the process: primary or secondary

ETIOLOGY
I.

DANG THERAPIST

D iabetic A lcohol N utritional G uillain-Barre syndrome T rauma H ereditary E ntrapment R enal/radiation A IDS/amiloid P araprotein/poria I nfection (leprosy) S ystemic/sarkoid T oxin

II. Based on course of disease, distribution, and EMG examination

A.

Acute, general
1.

Axonal, degeneration :
a. b.

Infections : Lyme, HIV, EBV, hepatitis, CMV. Miscellaneous : Porphyria, axonal Guillain-Barre syndrome, ICU neuropathy.

2.

Demyelination : Guillain-Barre syndrome, arsenic, infections, e.g.

HIV and diphtheria.

B. Chronic, generalized :
1.

Axonal degeneration :

Nutritional : Alcohol, folate, vitamin B6, B12, or E. Toxic : Phenytoin, vineristine, heavy metals, acrylamide, etc. Endocrine : DM, hypothyroidism Infection : HIV, Lyme Genetic : Charcot-Marie-Tooth (CMT) type II, Familial amyloidosis, Friedreichs ataxia, etc. Lipid Problems : Fabrys disease, Tangier disease, BassenKornzweing disease Other : Uremia, Vasculitis.

2. Demyelination :
a.

b.

Uniform Slowing on EMG : CMT types 1A, 1B, and X; myelin dysmetabolisme, e. g. Metachromatic leukodystrophy, Refsum disease, Krabbe disease. Nonuniform Slowing Infectious or inflammator : HIV, CIDP, multifocal neuropathy with conduction block. Paraprotein : Lymphoma, myeloma, POEMS syndrome (polyneuropathy with organomegaly, endocrinopathy, mprotein, and skin changes), Waldenstroms macroglobulinemia, MGUS (monoclonal gammopathy of uncertain significance), cryglobulinemia.

B. Mononeuropathy multiplex (multifocal or asymmetric)

1.

Axonal : a. Vascular : DM, Vasculitis (polyarteritis nodosa, Wegeners, giant cell arteritis, hypersensitivity), connective tissue dz, subacute bacterial endocarditis. b. Infectious or inflammatory : HIV, Lyme, Leprosy, VZV, hepatitis A, sarcoid. c. Neoplastic : Neurofibromatosis, leukemia, direct local invasion. d. Miscellaneous : Genetic, e.g. Inherited brachial plexus neuropathy; traumatic, e.g. multiple compressions

2. Demyelinating :
a. b.

c.

Inflammatory : Guillain-Barre; multifocal motor neuropathy with conduction block. Genetic : Hereditary neuropathy with liability to pressure palsies (HNPP) Multiple compressions

Generally, etiologies are divided as:

1.

2.
3. 4. 5. 6. 7. 8.

Metabolic disease Deficiency (nutritional) Alergy Intoxication Infection Hereditary Ischaemia Compression

CLINICAL FEATURES

Clinical features vary, based on:

etiology onset and course of disease pathological features location/distribution type of neurons which are attacked most

THERAPY
Therapy based on etiology (discussed in each type of neuropathy)

THANK

YOU

DIABETIC NEUROPATHY

A.

CLASSIFICATION (Green, AM.J.Med, 1999) Diffuse neuropathy

1. 2.

Distal symmetric sensorimotor polyneuropathy. Autonomic neuropathy a. Sudomotor neuropathy b. Cardiovascular autonomic neuropathy c. Gastrointestinal neuropathy d. Genitourinary neuropathy

3. Symmetric proximal lower limb motor neuropathy (amyotrophy).

B.

Focal neuropthy 1. Cranial neuropathy 2. Radiculopathy / plexopathy 3. Entrapment neuropathy 4. Asymmetric lower limb motor neuropathy (amyotrophy).

I. DIFFUSE NEUROPATHY a. DISTAL SYMMETRIC SENSORIMOTOR

POLINEUROPATHY

- Most common type of diabetic neuropathy

- Paresthesia/hipesthesia, numbness - Pain

- Initially in the distal part of distal extremity (fingers) upward - Stocking and glove pattern of sensory disturbance

Large neural fibers: - Disturbance of sensation of vibration, joint potition - Negative physiological reflexes - Ataxia DIABETIC TABES Motoric Disturbance - Motoric dysfunction atrophy

Neuropathic Pain :

Patients with uncontrolled blood glucose level):

-

Burning pain, pricky, electric sharp pain Allodynia, hyperalgesia, hyperpatia (stimulus evoked pain). Onset: immediately or slow.

Trias of Polineuropathy

Stocking and glove pattern of sensory disturbance Paresthesia, especially on the distal part of extremities Hyporeflex.

b. AUTONOMIC NEUROPATHY

Can exist itself or with symmetric polineuropathy

Sudomotor Dysfunction of Bone and Joint

Hyperhydrosis in the half upper part of body Anhydrosis in the half lower part of body dry skin and easy to develop fissure Sweating in the night Joint, especially genu/foot swelling but not painful (charcots joint) Bone hyperostosis

Cardiovascular

Postural hypotension
Change of heart rate response in valsava

manuevre

Digestion System

Decreased gustatory Weak instestine peristaltic: dysphasia, vomiting, epigastric burn, delayed gaster emptying (gastroparesis)

Intermittent diarrhea

Urogenital System:
Impotent: Common (35 75%) Increase with aging process, vascular complication (retinopatthy and diabetic neuropathy) (neurogenic, vascular and psychogenic factors)

Urogenital System:
Cystopathy : Develop in advanced stage Paient couldnt feel that his baldder was full (atonic bladder) Residual urine after mictie risk factor / can be recurrent.

c. SYMMETRIC PROXIMAL LOWER MOTOR NEUROPATHY

Also called as femoral diabetic amiotrophy or flexopit Specifically attacks man with DM type 2, decade 5 6 Associated with significant weight loss and bad blood glucose control Initially, sharp pain in upper extremities, symmetric or asymmetric Muscular atrophy Recover gradually if blood glucose was well controlled

II. FOCAL NEUROPATHY

a.

Cranial Nerves Neuropathy - Most common n.oculomotorius - Also can attack n.trokhlearis and abducens - Acute onset (frontal or periorbital pain) ptosis, diplopia. - Cause: nerve venous occlusion - Well controlled blood glucose recover in 3 months

b. Radiculopathy - Seldom - thoracoabdominal radicular pain - commonly in elderly - can attack motoric abdominal herniation

c. Entrapment Neuropathy - Carpal Tunnel Syndrome (n. medianus) - Tarsal Tunnel Syndrome (n.tibialis post) - Elbow Tunnel Syndrome (n. ulnaris)

Etiopathogenesis

Not yet clear

Every components of neuron can be disturbed

Pathology examination : any disturbance of neuron, axon, or myelin

Several theories:

1. Metabolic Theory/ hyperglicemia

Complicated Hypergcemia metabolism of poliol, formation of advanced glycation end product (AGE), oxidative stress, deficiency of essential amino acid such as gamma linolenic acid (GLA).

2. Vascular Theory

Decrease of blood flow in endo and epineural Increase of vascular resistance Decrease of PO2 Change in membran permeability Thickening of vascular endotel basal membran vascular, endo and epineural. ischaemia of neural tissue a lot of reactive oxygen (anaerob metabolism) Others: hyperviscosity, atherosclerosis, formation intraluminal fibrin. hypoxia and thrombocyte aggregation

3. Immunologic Mechanism

Antibody of anti-Gm1-gangliotide and anti fosfolipid antibody (anti-PLA) incerase the tendency of vascular thrombosis forming

4. Neurotrophyn Deficiency

Nerve growth factor (NGF) : has role in sustaining and regenerating ganglion, dorsal root, and symphatetic neuron, decrease of AGF. NT3 : has role in conduction of large fibers, motorneuron and sympathetic fibers, decerase of AGF. Insulin Growth Factor (IGF) : IGF and its receptors found in in whole central dan peripheral neuronal system. Role not clear yet.

Diagnosis
1. Diagnosis of DM Clinical features : poliuria, polidipsya, poliphagia, decrease of body weight with unclear cause Result of laboratory examination: - venous fasting blood glucose > 126 mg/dl - random blood glucose > 200 mg/dl

2. Neuropathy - There were clinical signs of neuropathy - Abnormality of nerve conduction - Abnormality in kwantitative sensory test and sensory autonomic function: dysfunction of hot-cold sensation, vibration, positional, glove-and-stocking type sensory deficit - Can be abnormal in motoric examination and decrease of achilles reflex

3. Autonomic Examination

Dry skin of the foot, there is fissure (sudimotor dysfunction) Charcot joint Heart rate response to valsava Orthestatic hypotension EKG: prolonged QR interval

4. EMG

Nerve Conduction Velocity (NCV) Amplitudo Motoric and Sensoric Distal Latency Demyelinating :
Decreased NCVKHS menurun Prolonged Motoric Distal Latency (MDL) Temporal Depression

Axonal Degeneration
Decreased amplitudo NCV and MLD normal or decrease slightly Potential denervation / fibrilation and positive to waves

4. Skin Biopsy

Management :
Management approach based on pathogenesis : 1. Aldose Reductase Inhibitor (ARI) - Inhibit the mechanism of ARI enzyme * Sorbitol and fructose not storaged * mencegah penurunan potensial redoksi 2. Asam linoleik

3. Aminoguaidin
Penghambat produk akhir AGE

4. Pemberian diet tinggi miyo-inositol

5. Human Intravenous Imunoglobulin Recombinan human NGF

Pemberian methylcobalamin 2 kali seminggu selama 12 minggu. Nyeri neuropatik diberi antidepresan trisiklik dan anti epilepsi Gastroparesis makan dan minum sedikit-sedikit dan frekuen, metoclopramide 3 kali 10 mg. Hipotonik kandung kemih diberi bethanecol 3 kali 10-30 mg atau kateterisasi intermiten. Inpotensi dgn sildenetil peroral 25-100 mg Hipotensi ortostatik diberi fludrocortison

Rehabilitasi medik / fisioterapi akupuntur, modulasi termal, trans cutaneus electris nerve stimulation (TENS) mengaktivasi proses nosiseptif endogen (endorfis) berefek menghilangkan rasa sakit.