NEUROPATHY for 5 th class students

1. NEUROPATHY for 5th class students Aim • To learn anatomical and some physiologic aspects of PN • Terminology. And definitions. • Epidemiology. • Etiology. • Pathology and pathogenesis. • Presentation. • Diagnosis and management • Clinical types.

2. NEUROPATHY for 5th class students

3. a 50 Years old man presents with difficulty in walking affecting mainly his fine tasks of feet over last 4 months duration which was preceded by 2 months of tingiling sensation and numbness affecting mainly feet to mid leg and hands • On examination : general was normal , medical –no abnormality neurological ---cerebral function was normal including speech • Cranial nerves were normal • UL &LL----there is wasting affecting distal muscle more in feet , absent ankle jerks bilaterally • Which system involved? • Which part? • DD

4. Terminology and definitions • Neuropathy : term used to describe any disorder that affect peripheral nerves , it may be: • Polyneuropathy—homogenous and simultaneous symmetrical affection of peripheral nerves (sensory or and motor with or without autonomic affections). • Mononeuritis simplex: focal involvement of a single nerve, usually due to a local cause such as trauma, compression, or entrapment. Carpal tunnel syndrome is a common example of a mono neuropathy in young woman specially during pregnancey. • Mono neuritis multiplex: simultaneous or sequential involvement of non contiguous nerve trunks. • loosely, this term can refer to multiple compressive mono neuropathies. • However, in its more specific meaning, it identifies multiple nerve infarcts due to a systemic vasculitis process that affects the vasa nervorum DD---DM , vasculitis , infection like HIV, paraproteinemia like Multiple myeloma and idiopathic

5. Epidemiology • More comprehensive data are available regarding the frequency of specific types of polyneuropathy or those with specific causes, such as diabetic polyneuropathy or inflammatory demyelinating polyneuropathy. • After 10 years, the number of patients who had nerve conduction abnormalities consistent with polyneuropathy reached 42 percent in the diabetic population versus 6 percent in controls. • The prevalence of polyneuropathy among patients with no recognized exposure to diseases or neurotoxic agents was 2 percent; • Diabetes mellitus was the most common risk factor, present in 44 percent of the patients with polyneuropathy. • The next most common risk factors were alcoholism, non-alcoholic liver disease, and malignancy. • clinical AIDS, 12 percent had evidence of a polyneuropathy

6. The prevalence of Guillain-Barré syndrome which is the common immune mediated neuropathy in most studies ranges from 0.4 to 1.7 per 100,000 population with a relatively even distribution throughout the world . • Guillain-Barré syndrome has been linked in some cases to preceding Campylobacter jejuni infection; the incidence may be much higher in areas of the world such as northern China where this is a common pathogen

7. Etiology • Inherited : Less common ; the best ex: Charcot marrie tooth(inherited polyneuropathy affecting only PN) or as part of more diffuse process and neuropathy is part of that disease like in Fredrich's ataxia and adrenal leucodystrophy • Acquired • Infection ; HIV , leprosy , Lyme disease. • Inflammatory ; immune mediated inflammatory reaction as • post infection in case of GBS and diphtheria • part of vasculitis as in SLE, Wegener's rheumatoid ----. • Metabolic : the commonest cause is Diabetic, uremia, porphyria and hepatic failure • Nutritional like B12 deficiency • Endocrine like hypothyroidism , ACROMEGALY. • Systemic disease: critically ill patients . amyloidosis • Drug and toxins :alcohol, chemotherapy exposure, or most heavy metals, produce a predominantly axonal disorder that can be acute, sub acute, or chronic, depending on the level and severity of the exposure . • Neoplastic direct infiltration or part of paraneoplastic. As in lymphoma • paraproteinemia as Multiple myeloma.

8. Pathogenesis and pathology • Electro physiologically it may be axonal or and demyelinating? • It may be only sensory NP (sensory fibers affected) • Motor neuropathy when motor fiber is affected • Mixed • With or with out autonomic dysfunction depending on the etiology Ex: • Diabetic polyneuropathy is generally considered predominantly axonal; however, variable degrees of demyelination are often present, at least electrophysiologically. The mechanism underlying the development of diabetic neuropathy is extremely complex and likely relates to inflammatory, metabolic, and ischemic effects. • Most common acute autoimmune neuropathies, namely Guillain-Barré syndrome, are predominantly demyelinating, and a variety of clinical and experimental data have implicated both humoral factors and cell-mediated immune phenomena, which damage myelin and/or the myelin-producing Schwann cells. axonal forms of this disease also exist.

9. Other systemic diseases generally also cause predominantly axonal polyneuropathies. Examples of these include the polyneuropathy associated with longstanding human immunodeficiency virus (HIV) infection, critical illness, amyloidosis, hypothyroidism, vitamin deficiencies, and Lyme disease. However, some important exceptions exist. As an example, polyneuropathy associated with monoclonal gammopathy is often demyelinating.

10. Presentation • The presentation of patients with polyneuropathy varies significantly depending upon the underlying pathophysiology. dependent upon the type of polyneuropathy (axonal versus demyelinating) and which classes of nerve fibers are most involved (motor versus sensory) • Injury tends to be related to axon length; thus, longer axons are affected first, resulting in symptoms that begin in the lower extremities then UL affected. • Sensory symptoms usually precede motor symptoms. Patients typically present with slowly progressive sensory loss and dysesthesias such as numbness, a burning sensation and pain in the feet, and mild gait abnormalities. Exam. Distal loss of sensation to pin prick, light touch, vibration, cold, and proprioception may also occur. • Motor: As the syndrome progresses, mild weakness of the lower legs and hand symptoms may begin, resulting in the classic "stocking and glove" distribution of sensory loss. The numbness may continue to extend proximally in severe cases.exam: distal muscle weakness(although weakness may affect proximal muscles to a greater extent in some individuals like GBS , DM) and wasting specially in chronic type with absent reflexes specially ankle jerk • Autonomic symptoms : postural hypotension , excessive seating , palpitation and bowel disturbance (constipation or and diarhea), impotence--- It can be pure sensory or motor and can be mixed with without autonomic dysfunction DM can give rise any type of neuropathy .

11. DIAGNOSIS • NCS: To confirm diagnosis even in asymptomatic case or with minimal S & S is by NCS which help also to determine the type of neuropathy as demyelinating versus axonal sensory or motor or mixed type . • Help to differentiate between single nerve affection like CTS or Mono neuritis multiplex and PNP. • CSF analysis indicated in GBS and chronic immune mediated demyelinating polyradiculopathy (CIDP) • Blood tests : for any metabolic disturbance like blood sugar , blood urea , LFT . • Serum B12 , thyroid function tests, screen for underlying malignancy(CXR ;US ; stool for occult blood ,mammography and tumor markers) or gammopathy screen ; screen for vasculitis ; serum for drugs or toxins------- • Genetic testing for hereditary neuropathy

12. MANAGEMENT • General treatment including reassurance , explanations , diet control in DM • pain control : drug of choice is antiepileptic drug like pregabalin ;gabapentin or TCA like amitriptylline or new SSRI duloxetine. • Treatment of the underlying cause like DM ,malignancy or correction of nutritional deficiency -----

13. Some clinical types- Diabetes • The common cause of neuropathy which can be classified in to • 1-symmetrical pure sensory or pure motor PNP , mixed sensory –motor-common type in 70% of neuropathy in DM proximal motor PNP autonomic neuropathy as isolated entity or with others) • 2-Asymmetrical: Mono neuritis cranialis like 6th or 3rd nerve palsy Mono neuritis simplex like radial ,Ulnar or median nerve palsy. Thoraco abdominal radiculopathy asymmetrical proximal motor NP=diabetic amyotrophy • Pathogenesis ? Mention before it can be seen in both types of DM more with long duration and poor control.

14. Gbs =The Guillain-Barré syndrome (GBS) is an acute monophasic illness causing a rapidly progressive polyneuropathy with weakness or paralysis. • Immune mediated PNP against peripheral myelin sheath ; 50 % gave history of URTI ; more worse if preceded by bloody diarrhea or when brain stem affection as exception called miller fisher variant( ataxia and ophthalmoplegia with areflexia). • Presentation : acute or sub acute flaccid areflexic ascending paralysis with lower facial motor neuron weakness in 50-70% of cases which can be bilateral , • Bulbar muscle can be affected ---bulbar palsy-sever form affecting respiration muscle specially 1st 2 week which may need ventilator assessment other wise death • Dysautonomia can occur in large no. of cases; which can cause death secondary to arrhythmia(tachy or brady) and conductions problem • Diagnosis: NCS and LP---albumin cytological dissociation? After 1st week. • Others to evaluate stool culture for polio , throat swab for diphtheria , PFT frequently and ECG tests and tilt table test for autonomic assessment. • Treatment ; general physiotherapy, prevent bed ridden complications admission to CCU when FVC less than 15 ml /kg • Specific lines Immunoglobulin 0.2-0.4 gm/kg daily for 3-5 days in 1st 1-2 week of onset • Plasmapharesis equally effective (3-5 session every other day to wash out antibodies) • Prognosis : it is self limiting ; complete recovery seen in 70-75% of cases. • 20% left with minor deficit and 5% die. • DD? HYPOKALEMIA , TRANSVERSE MYELITIS . POLIO . TICK PARALYSIS. DIPHTHERIA

15. CIDP-CHRONIC INFLAMMATORY DEMYELIATING pnp • Similar to GBS except it follow chronic course progressive or relapsing type with more deficits and improvement delayed to 6 months . • Cause ; unknown. • Presentation ;more than 4 weeks progressive weakness affecting proximal and or distal UL &LL with sensory symptoms in LL &UL .R. muscle ,dysphagia ;facial weakness less frequently seen • D; NCS AND CSF analysis. Tests to exclude secondary causes like HIV infection and malignancy. • Treatment ; Same to GBS with exception of effectiveness of steroid in CIDP.